Displaying One Session

Poster Area (Hall 4) Poster Display session
Date
29.09.2019
Time
12:00 - 13:00
Location
Poster Area (Hall 4)
Poster Display session 2 Poster Display session

Breast cancer, early stage (ID 6626)

Lecture Time
12:00 - 12:00
Speakers
  • Aleix Prat (Barcelona, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00
Poster Display session 2 Poster Display session

186P - Efficacy of dose-dense (DD) adjuvant chemotherapy (CT) in hormone receptor positive/HER2-negative early breast cancer (BC) patients (pts) according to immunohistochemically (IHC) defined luminal subtypes: An exploratory analysis of the GIM2 trial (ID 2551)

Presentation Number
186P
Lecture Time
12:00 - 12:00
Speakers
  • Benedetta Conte (Genova, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

DD adjuvant CT improves disease free survival (DFS) and overall survival (OS) in high-risk, hormone receptor positive BC. Luminal A and luminal B subtypes have different sensitivity to (neo)adjuvant chemotherapy; however, their role in predicting DD efficacy in clinically high-risk setting is uncertain. This exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015) evaluated DD efficacy according to IHC defined luminal subtypes.

Methods

In the GIM2 trial, pts with node-positive early BC were randomized to receive 4 cycles of (fluorouracil) epirubicin/cyclophosphamide every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel. Luminal A-like and luminal B-like BC were identified according to 13h St Gallen definition as having a Ki67<20% and a PgR>/=20% (luminal A-like), and a Ki67>/=20% and/or a PgR<20% (luminal B-like). Pts with HER2-positive BC were excluded. The efficacy of DD CT in terms of DFS and OS was compared between the two subtypes.

Results

Of 2,003 pts enrolled in the GIM2 trial, 401 had luminal A-like and 657 luminal B-like BC. After a median follow-up of 8 years, DFS was 81.1% (95% Confidence Intervals [CI] 76.6-84.7) and 70.6% (66.6-74.1) in luminal A-like and B-like BC, respectively; OS was 91.6% (88.1-94.1) and 85% (81.7-87.7), respectively. There was no significant interaction between treatment and luminal subtypes (pinteraction=0.416 for DFS and pinteraction=0.313 for OS); however, the effect of DD CT appeared to be greater in luminal-B like BC (see table below).

186P

8 year DFS SI8 year DFS DDHR (95% CI)
luminal A-like81.680.60.86 (0.56-1.30)
luminal B-like66.874.70.74 (0.55-0.98)
8 year OS SI8 year OS DD
Luminal A-like92.990.60.88 (0.47-1.67)
luminal B-like80.889.40.61 (0.40-0.93)

Conclusions

These long-term results confirm the prognostic value of IHC-defined luminal subtypes, with luminal B-like bearing a worse prognosis. In clinically high-risk, hormone receptor positive BC, luminal B-like subtype benefits more from DD CT both in terms of DFS and OS.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Lambertini: Honoraria (self), speaker honoraria: Theramex; Advisory / Consultancy: Teva. M. De Laurentiis: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene. S. De Placido: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Eli Lilly. F. Montemurro: Honoraria (self), speaker honoraria: AstraZeneca; Honoraria (self), speaker honoraria: Pfizer; Honoraria (self), speaker honoraria: Novartis; Honoraria (self), speaker honoraria: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses, speaker honoraria, travel grant: Roche. L. Del Mastro: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Roche-Genentech; Honoraria (self): Takeda; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

187P - High dose neo-adjuvant chemotherapy in triple-negative breast cancer with evidence of homologous recombination deficiency (HRD) (ID 3426)

Presentation Number
187P
Lecture Time
12:00 - 12:00
Speakers
  • Sonja B. Vliek (Amsterdam, Netherlands)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Subgroup analyses of randomized, controlled trials (RCTs) using high dose chemotherapy (HD) with autologous stem cell support (autoSCT) reveal a potential benefit of HD in patients with triple negative breast cancer (TNBC) and in tumors harboring features of HRD (Vollebergh et al, 2011). The phase III part of the neo-TN RCT, compared neo-adjuvant HD with conventional treatment (CONV) in BRCA1-like TNBC.

Methods

Patients with cT2-3N0-3M0 TNBC with HRD were randomized between HD or CONV after 3 courses of 2-weekly doxorubicin/cyclophosphamide (ddA60C600). CONV treatment consisted of another 3xddAC, or in case of an unfavorable response on MRI a switch to 3 cycles capecitabine800BID14-7/docetaxel75; after an amendment all patients switched to 3xcarboplatinAUC6/paclitaxel80weekly. The HD regimen consisted of a 4th course ddAC and 2 courses of cyclophosphamide3000d1/carboplatin400d1,2/ thiotepa250d2 both followed by autoSCT. Primary outcome was the Neo-adjuvant Response Index (NRI), secondary outcomes included overall (OS) and recurrence free survival (RFS).

Results

From 2010 to 2016, 122 patients were randomized (intention-to-treat). Median follow-up is 45 months. There was no significant difference in NRI between HD and CONV (mean NRI 0.78 versus 0.72, range 0-1, p = 0.41 Wilcoxon test). An NRI of > 0.7 was strongly associated with good prognosis (RFS of 97% [95%CI 93%-100%] versus 67% [95%CI 55%-82%] at 4 years). See Table for 4-years OS and RFS comparing HD with CONV. There were no treatment related deaths. However, 7 out of 55 patients who actually received HD did not complete HD mainly because of infections or allergic reactions.

187P

HD % (95%CI)CONV % (95%CI)HR (95%CI)p-value
All (n = 122)
4-yrs OS 4-yrs RFS92 (85-99) 92 (85-99)79 (69-91) 78 (68-89)0.43 (0.15-1.23) 0.41 (0.15-1.07)0.12 0.07
Stage III only (n = 35)
4-yrs OS93 (81-100)60 (39-93)0.14 (0.02-1.14)0.07

Conclusions

No significant efficacy differences were found between HD and CONV. The NRI is of prognostic value. Whether the HD regimen is promising, especially in very high risk BRCA1-like TNBC [HR = 0.14], requires additional data including a comparison with platinum treatment in all control arm patients.

Clinical trial identification

NCT01057069.

Legal entity responsible for the study

The authors.

Funding

The Dutch Cancer Foundation (KWF) and by the Schumacher Kramer Foundation.

Disclosure

S.C. Linn: Research grant / Funding (self), research support for patients fees in D-Care study: Amgen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Research grant / Funding (self): Genentech; Advisory / Consultancy: IBM; Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (institution), patients fees in TEAM 2b study: Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Speaker Bureau / Expert testimony, Fee for teaching, paid to institution: Bayer. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

188P - Risk factors for locoregional recurrence (LRR) after neoadjuvant chemotherapy: Pooled analysis of prospective neoadjuvant breast cancer (BC) trials (ID 3792)

Presentation Number
188P
Lecture Time
12:00 - 12:00
Speakers
  • Gustavo Werutsky (Porto Alegre, Brazil)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

LRR after neoadjuvant chemotherapy (NACT) for BC may impact patient’s outcome. This study aimed to evaluate the rates of LRR as first event after NACT and to identify independent predictors of LRR.

Methods

A total of 10075 women with primary BC and available follow-up from 9 prospective neoadjuvant trials were included in the pooled analysis. The main endpoint was cumulative incidence rates of LRR as first event after NACT; distant recurrence, secondary malignancy or death was defined as competing event. To identify predictors of LRR, surgery type, pathological complete response (pCR=ypT0 ypN0), BC subtypes and other risk factors were evaluated using Fine-Gray’s regression model. The two-sided significance level was set to α = 0.05.

Results

After a median follow-up in the entire cohort of 67 months (range 0-215 months), 959 (9.5%) LRRs as first event were observed. Age ( < =50 vs > 50 years; p < 0.001), clinical nodal status (cN- vs cN+; p < 0.001), tumour grade (G1-2 vs G3; p = 0.001), pCR (no vs yes; p < 0.001) and BC subtypes (HR+/HER2- vs HR+/HER2+, HR-/HER2+, TNBC; p < 0.001) but not surgery type (BCS vs mastectomy; p = 0.514) were significant independent predictors of LRR in multivariate analysis. LRR rates among BC subtypes were lower in pts achieving pCR vs non-pCR: HR+/HER2- (3.9% vs 5.9%; HR = 0.56 [95%CI 0.32-0.98]; p = 0.043); HR+/HER2 + (4.8% vs 8.1%; HR = 0.61 [95%CI 0.37-1.02]; p = 0.058); HR-/HER2 + (3.1% vs 14.8%; HR = 0.22 [94%CI 0.12-0.39]; p < 0.001) and in TNBC (4.2% vs 18.5%; HR = 0.25 [95%CI 0.18-0.35]; p < 0.001). Within the non-pCR subgroup, LRR rates were significantly higher in pts with HR-/HER2+ and TNBC vs HR+/HER2- BC (HR = 2.34 [95%CI 1.83-2.99]; p < 0.001 and HR = 3.02 [95%CI 2.54-3.60]; p < 0.001, respectively) as well as in pts treated with mastectomy than with BCS (HR = 1.22 [95%CI 1.06-1.1.41]; p = 0.007).

Conclusions

Young age, node-positive and G3 tumours as well as non-pCR status and TNBC were found to significantly increase the risk of LRR as first event after NACT. Pts with HR-/HER2+ and TNBC not achieving pCR were at highest risk of LRR. Hence, these BC subtypes might be considered for additional post-neoadjuvant treatment approaches.

Legal entity responsible for the study

German Breast Group (GBG).

Funding

Has not received any funding.

Disclosure

M. Untch: Honoraria (institution), non-financial support: Abbvie; Honoraria (institution), non-financial support: Amgen GmbH; Honoraria (institution), non-financial support: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), non-financial support: Celgene GmbH; Honoraria (institution), non-financial support: Daiji Sankyo; Honoraria (institution), non-financial support: Eisai GmbH; Honoraria (institution), non-financial support: Janssen Cilag; Honoraria (institution), non-financial support: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution): Lilly Deutschland; Honoraria (institution), non-financial support: Sividon Diagnostics; Honoraria (institution), non-financial support: MSD Merck; Honoraria (institution), non-financial support: Mundipharma; Honoraria (institution), non-financial support: Myriad Genetics; Honoraria (institution), non-financial support: Odonate; Honoraria (institution), non-financial support: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), non-financial support: Novartis; Honoraria (institution), non-financial support: Roche Pharma AG; Honoraria (institution), non-financial support: Sanofi Aventis Deutschland GmbH. C. Hanusch: Honoraria (self), Outside the submitted work: Roche; Honoraria (self), Outside the submitted work: Pfizer; Honoraria (self), Outside the submitted work: Novartis; Honoraria (self), Outside the submitted work: Celgene; Honoraria (self), Outside the submitted work: Lilly; Honoraria (self), Outside the submitted work: AstraZeneca. P.A. Fasching: Research grant / Funding (institution), The Work Under Consideration for Publication: Novartis; Research grant / Funding (institution), The Work Under Consideration for Publication: Biontech; Honoraria (self), The Work Under Consideration for Publication: Novartis; Honoraria (self), The Work Under Consideration for Publication: Roche; Honoraria (self), The Work Under Consideration for Publication: Pfizer; Honoraria (self), The Work Under Consideration for Publication: Celgene; Honoraria (self), The Work Under Consideration for Publication: Daiichi-Sankyo; Honoraria (self), The Work Under Consideration for Publication: TEVA; Honoraria (self), The Work Under Consideration for Publication: AstraZeneca; Honoraria (self), The Work Under Consideration for Publication: Merck Sharp & Dohme; Honoraria (self), The Work Under Consideration for Publication: Myelo Therapeutics; Honoraria (self), The Work Under Consideration for Publication: Macrogenics; Honoraria (self), The Work Under Consideration for Publication: Eisai; Honoraria (self), The Work Under Consideration for Publication: Puma; Research grant / Funding (institution), The Work Under Consideration for Publication: Cepheid. S. Seiler: Honoraria (self), presentations: Roche; Advisory / Consultancy: Amgen GmbH; Advisory / Consultancy: Hexal; Honoraria (self): Mundipharma; Non-remunerated activity/ies: Novartis. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. H. Tesch: Honoraria (self): Vifor; Honoraria (self): Roche; Honoraria (self): Amgen. C. Jackisch: Honoraria (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self): Roche. A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. T. Link: Honoraria (self): Amgen; Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Pharma Mar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche. J. Huober: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy: Abbvie. K. Rhiem: Honoraria (self): Tesaro; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca. S. Loibl: Honoraria (institution), Research grant / Funding (institution), The Work Under Consideration for Publication: Roche; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: AbbVie; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Amgen; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: AstraZeneca; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Celgene; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Novartis; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Pfizer; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Seattle Genetics; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Teva; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Vifor; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: PRIME; Honoraria (institution), Research grant / Funding (institution), Relevant financial activities outside the submitted work: Daiichi; Licensing / Royalties, Intellectual Property - Patents & Copyrights: EP14153692.0 pending. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

189P - Estimating radiotherapy-induced cardiovascular mortality in female breast cancer patients (ID 4044)

Presentation Number
189P
Lecture Time
12:00 - 12:00
Speakers
  • Mark De Ridder (Brussels, Belgium)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Radiotherapy halves the recurrence risk and reduces breast cancer death after breast sparing surgery, but it is associated cardiac morbidity and mortality (1). The EBCTCG data demonstrates an excess cardiac mortality rate ratio of 4,1% per increased Gray (Gy) whole heart dose (2). The aim of this study is to create a clinical applicable risk assessment model to predict 10-year cardiovascular mortality in female breast cancer patients.

Methods

By integration of the SCORE (Systematic COronary Risk Evaluation) risk charts and data of the EBCTCG we were able to develop cardiovascular mortality risk charts based on mean heart dose, age, systolic blood pressure, smoking-status and cholesterol for high- and low-risk regions in Europe, for contemporary mean heart doses of 2Gy, 4Gy and 8Gy.

Results

We will present tables showing the 10-year cardiovascular mortality based on mean heart dose, smoking status, age, systolic blood pressure and cholesterol for high- and low-risk regions in Europe. Below you find the risk table for 60-years old non-smoking women in low-risk regions. A 60-year old, non-smoking patient from France (low-risk region) with a cholesterol 220 mg/dl and a systolic blood pressure of 140 mmHg has a 10-year cardiovascular mortality risk of 1,0%, adding radiotherapy with a mean heart dose of 4Gy will increase it to 1,1% and doubling the heart dose to 8Gy results in a risk of 1,2%. In contrast, a 65 year old smoking patient living in Bosnia (high-risk region) with a cholesterol of 260 and a systolic blood pressure of 160 mmHg has a 10-year cardiovascular mortality risk of 13,0%, adding radiotherapy with a mean heart dose of 4Gy will increase it to 14,3% and doubling the heart dose to 8Gy results in a risk of 15,7%.

189P

Cholesterol: 200-250 mg/ml Mean Heart Dose
Cholesterol: 250-300 mg/ml Mean Heart Dose
SBP0Gy2Gy4Gy8Gy0Gy2Gy4Gy8Gy
180 mmHg3,03,23,33,64,04,24,44,9
160 mmHg2,02,12,22,42,02,12,22,4
140 mmHg1,01,11,11,22,02,12,22,4
120 mmHg1,01,11,11,21,01,11,11,2

Conclusions

Integrating cardiovascular risk tables and radiotherapy data are useful for patient individualized radiotherapy and cardiovascular prevention after breast cancer treatment. (1) Lancet 2011;378(9804):1707-16. (2) J Clin Oncol 2017;35(15):1641-1649.

Legal entity responsible for the study

The authors.

Funding

Vrije Universiteit Brussel.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

190P - 3-year follow-up of a phase III trial comparing the efficacy and safety of neoadjuvant and adjuvant trastuzumab and its biosimilar CT-P6 in HER2 positive early breast cancer (EBC) (ID 719)

Presentation Number
190P
Lecture Time
12:00 - 12:00
Speakers
  • Justin Stebbing (London, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

CT-P6 was approved by both US FDA and European Commission as a biosimilar to reference trastuzumab (RTZ). Here we report updated long term efficacy and safety.

Methods

549 patients with HER2 positive EBC were randomized 1:1 to CT-P6 (n = 271) or RTZ (n = 278) with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin and cyclophosphamide (Cycles 5-8). After surgery, patients received CT-P6 or RTZ monotherapy to complete a total of 1 year and were followed up to 3 years from enrollment of the last patient. Stratified Cox regression and Kaplan-Meier methods were used for time to event (TTE) analyses.

Results

528 patients (259 in CT-P6 and 269 in RTZ) were followed up. The median duration of follow-up was 39 months. Overall, the rates of disease-free survival (DFS) and overall survival (OS) were similar between CT-P6 and RTZ in both PPS and ITT set. The number of DFS events (42 [16.3%] in CT-P6 and 36 [13.8%] in RTZ) and OS events (18 [6.6%] in CT-P6 and 18 [6.5%] in RTZ) were comparable in ITT set. Median DFS and OS have not been reached due to an insufficient number of events. The mean LVEF was more than 60% in both groups, and no new cases of heart failure were reported during the follow-up period. Table. Summary of Long Term Efficacy Endpoints

190P

PPS
ITT set
CT-P6 n = 248RTZ n = 256CT-P6 n = 258RTZ n = 261
DFS rate
1 year (95% CI)0.95 (0.91 – 0.97)0.96 (0.93 – 0.98)0.95 (0.91 – 0.97)0.96 (0.93 – 0.98)
2 years (95% CI)0.87 (0.81 – 0.90)0.89 (0.85 – 0.92)0.87 (0.82 – 0.90)0.89 (0.85 – 0.93)
3 years (95% CI)0.82 (0.77 – 0.87)0.82 (0.75 – 0.88)0.83 (0.77 – 0.87)0.83 (0.76 – 0.88)
Hazard ratio (95% CI)1.23 (0.78 – 1.94)1.23 (0.78 – 1.93)
p-value0.38080.3807
CT-P6 n = 248RTZ n = 256CT-P6 n = 271RTZ n = 278
OS rate
1 year (95% CI)1.00 (1.00 – 1.00)1.00 (0.97 – 1.00)0.99 (0.97 – 1.00)0.99 (0.97 – 1.00)
2 years (95% CI)0.98 (0.95 – 0.99)0.98 (0.96 – 0.99)0.97 (0.93 – 0.98)0.98 (0.96 – 0.99)
3 years (95% CI)0.95 (0.91 – 0.97)0.94 (0.90 – 0.96)0.93 (0.90 – 0.96)0.94 (0.90 – 0.96)
Hazard ratio (95% CI)0.87 (0.42 – 1.82)1.10 (0.57 – 2.13)
p-value0.71810.7710
.

Conclusions

DFS and OS rates and cardiotoxicity at a median follow-up of 39 months support the similarity of CT-P6 and reference trastuzumab in early-stage breast cancer.

Clinical trial identification

NCT02162667.

Legal entity responsible for the study

Celltrion.

Funding

Celltrion.

Disclosure

J. Stebbing: Officer / Board of Directors, Editer-in-Chief: Oncogene; Advisory / Consultancy: Celltrion; Advisory / Consultancy: Vor Biopharma; Advisory / Consultancy: Benevolent AI; Officer / Board of Directors: BB Biotech Healthcare Trust; Officer / Board of Directors: Xerion Healthcare. Y. Baranau: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novatis. V. Moiseyenko: Speaker Bureau / Expert testimony: AstraZeneca. J. Pikiel: Travel / Accommodation / Expenses: Roche. A. Eniu: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Celltrion; Research grant / Funding (self): Pfizer. S.J. Lee: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Stock option: Celltrion. M.J. Kim: Full / Part-time employment: Celltrion. S. Kim: Full / Part-time employment: Celltrion. S. Park: Full / Part-time employment: Celltrion. J.H. Bae: Full / Part-time employment: Celltrion. F.J. Esteva: Advisory / Consultancy: Celltrion; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

191P - Adjuvant chemotherapy in elderly breast cancer patients: Pattern of use and impact on overall survival (ID 3595)

Presentation Number
191P
Lecture Time
12:00 - 12:00
Speakers
  • Axel Berthelot (Marseille, France)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ∼60% of deaths from BC occur in women aged 65 years and older. The management of elderly women with early BC requires careful evaluation of risks and benefits of available treatment options. Clinical trials for elderly patients in the adjuvant setting are lacking, and efficacy results obtained in general population cannot be directly extrapolated to elderly patients without specific evidences. Therefore, we examined factors associated with the prescription of adjuvant chemotherapy (aCT) and the impact of this treatment on overall survival (OS) in a large cohort of patients aged 65 years and older.

Methods

Patients were retrospectively identified from a large cohort of 23,134 early BC patients who underwent primary surgery in 18 academic centres between 1990 and 2014. A binary logistic regression was built to identify the factors associated with aCT administration. The impact of aCT on OS was analysed using a multivariate Cox regression model including age, histology, grade, tumour size, lymphovascular invasion (LVI), nodal status and endocrine therapy (ET) and endocrine receptors (ER). A propensity score-based matching analysis was performed.

Results

Of 6605 patients aged 65 years and older, 1493 received aCT (22.6%). Administration of aCT was predominantly associated with macroscopic lymph node involvement (LNi) and ER-negative status but common predictors, such as age < 80 years, ductal histology, tumour size ≥ 20mm, ET and tumour grade were also found as statistically significant. In a Cox model including age, histology, LVI, tumour size, LNi, ET, ER and grade, aCT was significantly associated with better OS (HR 0.71, 95% CI 0.58 to 0.86; p < 0.001). Ten-year OS estimates in case-matched patients for propensity score analysis were 76.8% (95% CI 76.6 to 77.1) in the aCT group vs. 61.5% (95% CI 61.3 to 61.7) without aCT (p < 0.0001). Interestingly, this benefit was maintained in the over-80s subgroup.

Conclusions

The factors associated with aCT use in the elderly are similar to those usually found in younger age groups. By highlighting an OS benefit, even in the “very old” subgroup, our results may help clarifying the role of aCT in elderly patients.

Legal entity responsible for the study

Houvenaeghel Gilles.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

192P - Carboplatin-containing neoadjuvant chemotherapy for triple negative breast cancer (TNBC): A propensity score-matched study (ID 3992)

Presentation Number
192P
Lecture Time
12:00 - 12:00
Speakers
  • Maria Vittoria Dieci (Padova, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The value of adding carboplatin (Cb) to neoadjuvant chemotherapy for TNBC is debated. Current evidence supports the association between Cb use and increased pathological complete response (pCR) rate. However, treatment schedules and doses adopted in randomized trials were not always consistent with those used in clinical practice.

Methods

Clinicopathological data of TNBC (ER & PgR<10%) patients treated at our Institution with neoadjuvant anthracycline and taxane (AT) with or without Cb were collected. Propensity score was used to control selection bias. Variables considered for matching were: age, Ki67, cT, cN, histologic grade, histotype, BRCA status. Tumor infiltrating lymphocytes (TILs) were not used as matching variable since data were lacking for 39% of cases. The distribution of TILs in the two matched groups was similar (p = 0.669). Binary logistic regression was used to test the association of Cb treatment with pCR (ypT0/is ypN0). Cox regression was used for survival analyses.

Results

166 patients were included: 61% treated with AT, 39% with AT+Cb (all patients in this group received Cb AUC2 weekly administered concomitantly to the taxane segment). Main characteristics: median age 50 yrs, ductal histology 93%, grade 3 90%, cT > 2cm 86%, cN + 57%, median TILs 10%, median Ki67 60%, BRCA mutated 10%. After propensity score matching, pCR rate was significantly higher for AT+Cb vs AT: 52% vs 31% (OR 2.39 95%CI 1.04-5.50, p = 0.040). In multivariable analysis, treatment with AT+Cb maintained an independent association with pCR: OR 2.51 95%CI 1.03-6.11, P = 0.043. The achievement of pCR was significantly associated with improved disease-free survival (HR 0.16, 95%CI 0.06-0.45). No difference in DFS was observed comparing AT+Cb vs AT: HR 0.99, 95%CI 0.44-2.25.

Conclusions

We confirmed in a clinical practice setting the association of Cb-containing neoadjuvant chemotherapy with higher pCR rates. Additional data are needed to clarify the impact on long-term survival. These data support the conditional positive recommendation for Cb inclusion in neoadjuvant chemotherapy for TNBC provided by the Italian Association of Medical Oncology Guidelines on Breast Cancer.

Funding

Has not received any funding.

Disclosure

M.V. Dieci: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genomic Health.

V. Guarneri: Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Eli Lilly; Speaker Bureau / Expert testimony: Novartis; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

193P - Impact of adjuvant trastuzumab emtansine (T-DM1) on incidence of metastatic breast cancer (mBC): An epidemiological model of patients with HER2-positive breast cancer (BC) who did not achieve pathological complete response (pCR) after neoadjuvant treatment (non-pCR) (ID 3477)

Presentation Number
193P
Lecture Time
12:00 - 12:00
Speakers
  • Mellissa Y. Williamson (South San Francisco, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Progression from early BC (eBC) to mBC creates a substantial burden for pts and healthcare systems. The KATHERINE trial showed adjuvant T-DM1 reduced the risk of disease recurrence or death by 50% vs trastuzumab (T) in pts with HER2-positive eBC with residual disease after neoadjuvant tx. The population level impact of T-DM1 on preventing relapsed mBC cases of HER2-positive, non-pCR eBC in 5 European countries (EU5) was estimated.

Methods

An epidemiological model was developed and data from observational and clinical trial studies were used to inform BC variables (Table). Weighted averages of non-pCR rates by neoadjuvant tx and hormone receptor (HR) subtype were calculated and extrapolations from KATHERINE data were used to model disease progression and death.

193P Epidemiology model variables and sources to determine prevented relapsed mBC cases over the time period 2020-2029

VariableDefinitionSource
BC incidenceAll incident cases of BCNational Cancer Registries for EU5*
eBC stage HER2/HR statusStage I–III HER2-positive, HR-positive, and HR-negativePublished literature, SEER data
HER2-positive neoadjuvant tx rateRate of tx with T or T + pertuzumabESMO guidelines, syndicated reports, and SEER data
HER2-positive neoadjuvant-treated non-pCRHER2-positive who do not achieve pCR after neoadjuvant tx by tx regimen and HR statusSystematic literature review of observational studies, NeoSphere and KRISTINE trials
Relapsed mBC incidenceExtrapolated disease-free survival and overall survival curvesKATHERINE trial

EU5 = France, Germany, Italy, Spain, United Kingdom (UK) ESMO, European Society for Medical Oncology; SEER, Surveillance, Epidemiology, and End Results.

Results

Projected incidence of HER2-positive eBC in EU5 increased from 36,966 to 39,039 pts between 2020 -2029. Annual population eligible for adjuvant T-DM1 tx was stable at approximately 10,000 pts over the study time period. Total cases of mBC prevented with adjuvant T-DM1 from 2020 -2029 is projected to increase from 46 to 1732 with a cumulative total of 10,139 or 27% of total projected incident-relapsed mBC cases among pts with HER2-positive, non-pCR eBC. At year 10 (2029), the model projects 3798 pts prevented from developing mBC with T, thus a 46% decrease with TDM-1 relative to T. Findings were similar across EU5. Modeling estimates may not consider shifts in incidence or reflect actual practice or events occurring outside of the study period.

Conclusions

Model outputs show a reduction of mBC due to T-DM1 beyond the maximum impact of T in eBC in EU5, thereby changing the epidemiology of HER2-positive BC over time, illustrating an even further decrease in current clinical and economic burden of this disease in these high-risk pts.

Editorial acknowledgement

Purvi Shah, MD, of Ashfield Healthcare Communications (a UDG Healthcare plc company), supported by F Hoffmann-La Roche Ltd/Genentech, Inc.

Legal entity responsible for the study

F Hoffmann-La Roche Ltd/Genentech, Inc.

Funding

F Hoffmann-La Roche Ltd/Genentech, Inc.

Disclosure

M.Y. Williamson: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Tomar: Full / Part-time employment: ZS Associates International Inc. G.S. Jhuti: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. C. Revil: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann -La Roche Ltd. A. Kotzeva: Full / Part-time employment: F. Hoffmann -La Roche Ltd. K. Gururaj: Full / Part-time employment: ZS Associates International Inc.

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Poster Display session 2 Poster Display session

195P - Chemotherapy (CT)-induced anaemia in patients (pts) treated with dose-dense regimen: Results of the prospectively randomised anaemia substudy from the neoadjuvant GeparOcto study (ID 3928)

Presentation Number
195P
Lecture Time
12:00 - 12:00
Speakers
  • Hans Tesch (Frankfurt am Main, Germany)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Use of parenteral (IV) ferric carboxymaltose (FCM) has been shown to be an efficient treatment of iron deficiency anaemia that can prevent blood transfusion. This substudy compared use of FCM with physician’s choice (PhCh) anaemia therapy in breast cancer (BC).

Methods

In GeparOcto trial pts with primary BC were randomised to receive sequential, intensified, dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) or weekly paclitaxel/liposomal doxorubicin +/- carboplatin (PM(Cb)) (Schneeweiss et al. Eur J Cancer). Pts with anaemia grade ≥2 (haemoglobin (Hb)<10g/dl), transferrin saturation (TSAT) ≤20% and serum ferritin <300ng/ml (amended to < 600ng/ml) were randomised to receive weekly FCM or PhCh (no treatment, oral iron, erythropoiesis-stimulating agent, or both) anaemia therapy. Stratification factors were CT arm (iddEPC vs PM(Cb)) and planned PhCh. Primary objective compared the frequency of pts achieving Hb ≥ 11g/dl at 6 wks of therapy between both arms. Main secondary objectives were median time to achieve Hb ≥ 11g/dl and changes in iron parameters at baseline vs different time points. It was planned to include 184 pts per arm using 2-sided exact Fisher test, with α = 0.05 and power 80%.

Results

Less than anticipated pts had CT-induced anaemia. 125 pts were randomised (62 in FCM, 63 in PhCh arm). Median age was 46 years (range 26-66); median levels of Hb, serum ferritin and TSAT were 9.6 (7.6-11.8)g/dl, 201 (3.0-551)ng/ml and 14.0% (4.0%-76.0%), respectively. After 6 wks, overall 40 (32.0%) pts (22 in FCM and 18 in PhCh arm; p = 0.447) reached Hb ≥ 11g/dl. Median time to achieve Hb ≥ 11g/dl was 9.0 wks with FCM vs 10.6 wks by PhCh. Median Hb changes vs baseline were comparable in both arms during the treatment. 2 pts in FCM and 5 in PhCh arm (p = 0.246) received blood transfusions until 6 wks of therapy.

Conclusions

This is the first study investigating IV iron treatment for dose-dense CT-induced anaemia in BC. 32% of pts reached Hb ≥ 11g/dl at 6 wks. FCM treatment was not different than PhCh for anaemia therapy.

Clinical trial identification

NCT02125344.

Legal entity responsible for the study

German Breast Group (GBG).

Funding

The anaemia supportive treatment substudy was financially supported by Vifor Pharma Ltd and the GeparOcto trial by Amgen, Roche and TEVA.

Disclosure

H. Tesch: Honoraria (self): Vifor; Honoraria (self): Roche; Honoraria (self): Amgen. S. Loibl: Honoraria (institution), Research grant / Funding (institution): Roche; Honoraria (institution), Research grant / Funding (institution): Amgen GmbH; Honoraria (institution), Research grant / Funding (institution): AstraZeneca; Honoraria (institution), Research grant / Funding (institution): Celgene; Honoraria (institution), Research grant / Funding (institution): Novartis; Honoraria (institution), Research grant / Funding (institution): Pfizer; Honoraria (institution), Research grant / Funding (institution): Seattle Genetics; Honoraria (institution), Research grant / Funding (institution): Teva; Honoraria (institution), Research grant / Funding (institution): Vifor; Honoraria (institution), Research grant / Funding (institution): PRIME; Honoraria (institution), Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. V. Möbus: Honoraria (self): Amgen; Honoraria (self): Celgene; Honoraria (self): Myelotherapeutics; Honoraria (self): AstraZeneca. M. Untch: Honoraria (institution), Non-remunerated activity/ies: Abbvie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution), Non-remunerated activity/ies: Janssen Cilag; Honoraria (institution), Non-remunerated activity/ies: Lilly; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics; Honoraria (institution), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Novartis; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Lilly; Honoraria (self): AstraZeneca. S. Seiler: Honoraria (self), presentations: Roche; Honoraria (self), Advisory / Consultancy: Amgen GmbH; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Mundipharma; Advisory / Consultancy: Novartis. P.A. Fasching: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Biontech; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): PUMA; Research grant / Funding (institution): Cepheid. K. Rhiem: Honoraria (self): Tesaro; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer. J. Huober: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: MSD Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Travel / Accommodation / Expenses: Abbvie. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. T. Link: Honoraria (self): Amgen; Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Pfizer; Non-remunerated activity/ies: Pharma Mar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self): MSD Oncology; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche. A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): MSD Oncology; Honoraria (self): Tesaro; Honoraria (self): Lilly. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

196P - The clinical impact of adjuvant dose-dense sequential chemotherapy (dds-CT) in patients with high-risk operable breast cancer (BC): Pooled analysis of 6 clinical trials (ID 2184)

Presentation Number
196P
Lecture Time
12:00 - 12:00
Speakers
  • Elena Fountzila (Thessaloniki, Greece)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The principles of dose-dense (dd) and sequential (s) chemotherapy (CT) were introduced in the adjuvant setting by HeCOG in 1997. We aimed to explore the long-term clinical benefit and safety of treatment of adjuvant dds-CT in patients (pts) with high-risk BC.

Methods

We performed a pooled analysis from 6 HeCOG-initiated clinical trials (3 randomized and 3 observational). Patients with operable, early-stage breast cancer received adjuvant treatment with epirubicin, taxane and cyclophosphamide/methotrexate/ fluorouracil (CMF), except from 297 patients included in one study who did not receive taxanes. Granulocyte colony-stimulating factor was given prophylactically with all treatment regimens. The primary study endpoint was 10-year disease-free survival (DFS) rate.

Results

Between 06/1997 and 04/2013, 4,767 pooled pts were treated with dds-CT (median age 52.9, range 20.9-82.7, postmenopausal: 54%). Patients presented with Hormone receptor (HR)-positive/HER2-negative tumors (56%), HER2-positive tumors (29%) or triple negative breast cancer (TNBC, 15%). Overall, 92.2% of pts completed CT according to study protocol. Grade 4 adverse events were recorded in 356 (8%) pts, mostly neutropenia (81%). Grade 3-4 cardiac adverse events were reported in 6 (0.1%) pts. Six pts succumbed from toxicity during CT including febrile neutropenia (2 pts), acute myocardial infarction (1 pt), infection (1 pt), pulmonary embolism (1 pt) and acute respiratory failure (1 pt). In total, 134 (3%) pts were diagnosed with a secondary cancer; 126 (2.8%) with solid tumors and 16 (0.4%) with a hematologic malignancy. Median follow-up time was 8.9 years (95% CI 8.8-9.1). The 10-year DFS rate was 76% for pts with HR-positive/HER2-negative tumors, 73% with TNBC and 74% for those with HER2-positive tumors (62% and 82% in the pre- and post-trastuzumab era, respectively (p < 0.001).

Conclusions

dds-CT with epirubicin, taxane and CMF in the adjuvant setting was well-tolerated and was associated with favorable clinical outcomes.

Legal entity responsible for the study

Hellenic Cooperative Oncology Group (HeCOG).

Funding

Hellenic Cooperative Oncology Group (HeCOG).

Disclosure

E. Fountzilas: Travel / Accommodation / Expenses: K.A.M ONCOLOGY / HEMATOLOGY; Travel / Accommodation / Expenses: Merck; Shareholder / Stockholder / Stock options: Deciphera. G. Pentheroudakis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution): Roche; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Amgen; Leadership role, Research grant / Funding (institution): Boehringer; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Merck; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Leadership role: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Leadership role: Enorasis. C. Christodoulou: Advisory / Consultancy: Merck; Advisory / Consultancy: Genesis Pharmaceuticals; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Sanofi. A. Koutras: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Genesis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Amgen. E. Samantas: Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Asta-Zeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche Hellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer. P. Papakostas: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck; Advisory / Consultancy: Genesis Pharmaceuticals. A. Psyrri: Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: MSD; Research grant / Funding (institution): Kura. P.A. Kosmidis: Honoraria (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Genesis. A. Koumarianou: Advisory / Consultancy: Genesis Pharma; Honoraria (self): Pfizer; Speaker Bureau / Expert testimony: Roche; Research grant / Funding (self): Merck; Travel / Accommodation / Expenses: MSD. E. Razis: Honoraria (self), Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses: Genesis Pharmaceuticals; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Genekor. H. Gogas: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Pierre-Fabre. G. Fountzilas: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

197P - The efficacy of preoperative breast cancer chemotherapy without anti-HER2-targeted treatment: Single center experience in setting of no reimbursement in Poland (2011-2015) (ID 3902)

Presentation Number
197P
Lecture Time
12:00 - 12:00
Speakers
  • Agnieszka Badora-Rybicka (Gliwice, Poland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Targeted anti-HER2 therapy is a keystone in radical breast cancer therapy. In Poland preoperative use of trastuzumab was not reimbursed until 2016 and pertuzumab is still not covered. Moreover, adjuvant use of trastuzumab was not covered for patients with stage IIIB-C breast cancer. The aim of the study was to analyse of the subset of patients with HER2-positive breast cancer who were treated preoperatively in s center in Poland without use of anti-HER2 medications to analyse their prognosis compared to other breast cancer subtypes.

Methods

We reviewed the records of patients enrolled to the prospective study of prediction of chemotherapy response (MILESTONE-BreastPred). All patients were enrolled between 2011—2015, with intent of preoperative breast cancer chemotherapy, mainly by AC-P or TAC regimens. In the whole group PET/CT was used as an method of staging.

Results

197P

SubtypeHER2-positiveTNBCLUM B HER2-negativeP
numer of patients11987160
median age4742.746.6n.s.
% G366.486.147.40.001
% N + 74.860.967.5n.s.
% CSIII56.242.938.80.048
% de novo CSIV11.93.58.1n.s.
% inoperable after chemotherapy [%]17.710.310n.s.
% pCR32.6539.7420.140.005
% 5-year PFS47.270.668.30.001
median PFS [mo]56.7NR92.90.001

Conclusions

HER2-positive breast cancer in Polish population is at presentation more advanced than other subtypes, and despite relatively high pCR rate, has poor prognosis, when treated without sufficient anti-HER2 therapy. Prognosis in HER2-positive breast cancer in the analysed subgroup of Polish patients was poorer than in TNBC. The results underline the importance of treatment according to international guidelines and speak in favour of including anti-HER2 therapy preoperatively. The study was supported by the Polish National Center of Research and Development MILESTONE project – Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015.

Legal entity responsible for the study

The authors.

Funding

the Polish National Center of Research and Development MILESTONE project – Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

198P - A multicentre, international neoadjuvant (NA), randomized, double-blind phase III trial comparing fulvestrant to a combination of fulvestrant and palbociclib in patients with operable luminal breast cancer (SAFIA Trial) (ID 4733)

Presentation Number
198P
Lecture Time
12:00 - 12:00
Speakers
  • Jean-Marc A. Nabholtz (Riyadh, Saudi Arabia)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

NA chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2- BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs.

Methods

This is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle-East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/- Goserelin) compared to ET alone as NA therapy of HR+/Her2- operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease-free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies.

Results

A total of 400 pre and post-menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) < 31 are treated with Fulvestrant (500 mg Day (d.) 1, 14, 28 then q. 28 d. (+/- Goserelin 3.6 mg q.28 d.) for 4 months. Pts with responding/stable disease are then randomized in double blind fashion to Fulvestrant (+/- Goserelin) with either Palbociclib 125mg po daily 3 weeks/4 or placebo. Four additional cycles are delivered before surgery The trial was initiated in 2018. As of April 2019, 196 patients have been enrolled. The majority of them (60%) are pre/peri menopausal. The mean age is 50.5 years (range: 25-83). RS of < 31 was reported in 75% of cases. So far, 96 pts have completed the induction ET and were randomized to ET with or without Palbociclib. End of accrual is expected by end of 2019.

Conclusions

SAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo-adjuvant strategy without CT in luminal operable BC.

Clinical trial identification

NCT03447132.

Legal entity responsible for the study

International Cancer Research Group (ICRG).

Funding

Pfizer, AstraZeneca and Genomic Health.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

199P - Outcome of non-metastatic male breast cancer: 222 patients (ID 5227)

Presentation Number
199P
Lecture Time
12:00 - 12:00
Speakers
  • Ulku Yalcintas Arslan (Ankara, Turkey)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

There are limited data for Male breast carcinoma(MBC) in the era of adjuvant taxanes and trastuzumab. We have previously reported outcome of non-metastatic 113 patients(pts) with MBC. We aimed to evaluate outcome of the changing adjuvant systemic treatment practices and survival in operable MBC.

Methods

The medical records of 261 MBC pts followed between 1986-2018 at 8 cancer center were reviewed retrospectively. 222 patients had non-metastatic MBC at the time of diagnosis were included in current study.

Results

Median age was 61(29-91) years. Median follow-up 55(1-275)months(mths). %91 of the pts had invasive ductal carcinoma. Also, 30.6% had T3-4 tumors. About half of study group had axillary lymph node-positive tumors. The proportion of positivity of ER, PgR and HER2 status were % 82.5, 73.1 and %18.4. Ten pts had TN MBC. 55 of pts had at least one comorbid chronic illness. 83.9 % of pts had modified radical mastectomy(MRM). 79.9% of pts received adjuvant radiotherapy. Adjuvan hormonotherapy were advised for %78.8, whereas adjuvant chemotherapy(CT) for 71.2 % of the pts(CMF 10.6%, adjuvant trastuzumab %7.5 and antracycline and/or taxane based 81.9% ). 9 HER2-positive pts had no adjuvant CT. Locoregional and/or distant recurrence rate was 36.9%. 77 (34.5%) pts died during follow-up. 52 of them died from metastatic breast cancer. 5-year disease-free survival(DFS) was found to be 66.6 % whereas overall survival(OS) was 73.5 %. Patients with stage I/II tumor were significantly longer DFS as compared to pts had stage III MBC( median not reached vs 78 mths, P<.001). Also, the latter group of pts had worse OS than the first group ( median 103 vs 153 mths, P=.030). Median DFS for pts had MRM was significantly better than patients had limited surgery (one-third of those pts had no axillary dissection)(118 vs 57 mths, P=.002). Two HER2-positive pts treated with adjuvant trastuzumab containing regimen had breast cancer recurrence(n = 11) and alive whereas 9 of 19 pts treated other chemotherapy regimen (All but 2 anthracycline and/or taxane based) had experienced the disease relapse and 7 of them died from MBC.

Conclusions

Although the adjuvant use of anthracyclines /taxanes and trastuzumab for MBC have increased in the last 10 years, stage at diagnosis is still important prognostic factor for survival in MBC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

200P - Effects of delayed initiation of adjuvant trastuzumab for non-metastatic, HER2 positive breast cancer in a limited resources setting: ML25232 study final results (ID 5943)

Presentation Number
200P
Lecture Time
12:00 - 12:00
Speakers
  • Samir Beslija (Sarajevo, Bosnia and Herzegovina)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

An optimal adjuvant treatment of HER2 positive breast cancer includes the initiation of trastuzumab within 6 months after the surgery. However, due to limited resources and waiting lists, this timeframe is often exceeded in developing countries. We previously reported short-term outcomes of a time-optimal versus delayed postoperative initiation of trastuzumab in women with HER2 positive, non-metastatic, neoadjuvant naïve breast cancer. Here, we report an extended follow-up, summarizing outcomes of our cohorts.

Methods

We included 223 consecutive women with surgically treated, non-metastatic, neoadjuvant naïve, HER2 positive breast cancer from 2009 to 2011, from four institutions in Bosnia and Herzegovina. Patients were assigned to a time-optimal group (TOG), or a delayed group 1 (DG1), or a delayed group 2 (DG2), depending on whether their adjuvant trastuzumab was initiated 6 months, or 6-12 months, or more than 12 months after the surgery, respectively. A cut-off point for the follow-up was January 2019. We compared clinical outcomes between the groups, taking into account lymph node status.

Results

The patient’s median age was 55 (range 27-80) years. Mean follow-up period was 67 (range 4-109) months. Node-negative disease was found in 38.6% patients overall. 37% (TOG) patients received trastuzumab within 6 months, while 41% (DG1) received it within 6-12, and 22% (DG2) more than 12 months after their surgery. A higher number of node negative patients was found in the DG2 group compared to the TOG and DG1 groups (48%, 35%, and 36% respectively). 5-year DFS rate was 70.73% (TOG), 67.03% (DG1), and 62.00% (DG2). The OS rate was 78.05% (TOG), 75.82% (DG1), and 74.00% (DG2).

Conclusions

From the above, a conclusion can be made that patients with time-optimal initiation of adjuvant trastuzumab therapy had a higher 5-year DFS and OS rate compared to the delayed treatment initiation groups. Results of the DG1 and the DG2 group indicate that trastuzumab therapy shows a persistent benefit even if administered with a delay. Higher DFS and OS rates in the DG2 group could be explained by a higher number of node-negative low-risk, patients in this group.

Legal entity responsible for the study

The authors.

Funding

Roche.

Disclosure

S. Beslija: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. T. Ceric: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. B. Hasanbegovic: Advisory / Consultancy: Roche. A. Pasic: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

201P - Final results of scalp cooling for hair preservation: A single- institution prospective study (ID 1725)

Presentation Number
201P
Lecture Time
12:00 - 12:00
Speakers
  • Dario Loparco (Brindisi, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The cancer treatments bring with it body image challenges, causing low self-esteem and contributing to worsen the quality of life. Chemotherapy (CT)-induced hair loss (HL) is one of the most emotionally distressing side effects of several breast cancer (BC) treatments. The DigniCap system (DCS), using the scalp cooling system, has been shown to reduce CT-induced alopecia (A) in a multicenter prospective trial. The purpose of this prospective observational study was to describe our experience.

Methods

Two DCS device are available at the Brindisi Oncology Dpt. From February 2016 and January 2019, 158 consecutive early stage BC pts who received anthracycline and/or taxane-based treatment were enrolled, post local Ethics Committees approval. A nurse and a psychologist were dedicated for these pts. Success of scalp cooling was defined according to the Dean’s scale: G0=no HL; G1 < 25% HL; G2=25–50% HL; G3=50–75% HL; G4 >75% HL.

Results

A total of 158 women were included in the following treatment cohorts: n = 70 (44.30%) received 4 courses of EC (epirubicin at 90 mg/m2 and cyclophosphamide (c) at 600 mg/m2 intravenously (IV) on day 1, with 21 days between cycles) followed by 12 courses of paclitaxel (P) 80 mg/m2 IV once a week (w); n = 56 (35.4%) received only 4 courses of EC, n = 28 pts (17.7%) P (80 mg/m2 IV once a w) and concurrent trastuzumab (2 mg/Kg IV; loading dose 4 mg/kg) for 12 consecutive doses and n = 4 (2.6%) pts received 4 courses of TC (docetaxel at 75 at 90 mg/m2 and c at 600 mg/m2 IV on day 1, every three w. Median age was 49 years (range 31-74). Overall success was observed in 115 pts (72.8%). Full preservation of the hair (G0) was observed in 37 pts (23.4%), G1 in 47 pts (29.7%) and G2 in 31 pts (19.6%). Most frequent scalp cooling-related symptoms were coldness (n = 129, 81.6%), neck pain (n = 83, 52.2%) and headache (n = 113, 71.5%). Overall, 14.6% (n = 23) of pts discontinued DCS because of unsatisfactory hair preservation (n = 11, 7.0%) and cold discomfort (n = 12; 8.4%). Furthermore we observed a hair growth when DCS was continued for pts with A G3 – G4.

Conclusions

Our results confirmed and reinforced previous evidences, showing that DCS is a good chance to prevent A during CT with anthracycline and/or taxane-based regimen and supported the wider use to all women with early stage BC.

Legal entity responsible for the study

Saverio Cinieri.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

202P - Adjuvant systemic therapy in women with early breast cancer and intermediate prosigna ROR scores: Is chemotherapy use declining? Evidence from a large practice (ID 3713)

Presentation Number
202P
Lecture Time
12:00 - 12:00
Speakers
  • Lowell L. Hart (Winston Salem, FL, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Decision making on adjuvant systemic therapy in women with primary node-negative, HR+ breast cancer and intermediate risk scores on a molecular tumor profile has often been difficult, and may be based also on additional clinical factors such as age, tumor size and grade. In mid-2018 new level 1 evidence on the lack of additional benefit with chemo-hormonal therapy versus hormonal therapy for most of these patients emerged. We sought to determine if systemic adjuvant therapy choices have changed in a large community practice of over 200 medical oncologists in the U.S. using in-house tumor testing with the Prosigna PAM 50 assay. There is robust clinical evidence on recurrence risk estimation with PAM 50. Data from the ABCSG-8 estimates distant RFS of 91.3% at ten years in the intermediate risk group treated with hormonal therapy alone. Decreased chemo use would lead to decreased therapy-related toxicity and probable healthcare cost savings.

Methods

We compared Prosigna ROR results in individual postmenopausal women with HR+, node- primary breast cancers from the period 9/17 through 6/18, with the period 6/18 through 3/19. Approximately 800 total tests were run from one large practice in the U.S. About 20% fell into the intermediate score range We compared the number of patients receiving adjuvant chemohormonal therapy versus hormonal therapy alone or no systemic therapy. Physicians were polled as to whether their decisions were influenced by the ROR score, clinical factors, or both.

Results

During the period studied, the percentage of patients with intermediate ROR scores receiving adjuvant therapy declined. Physicians based their decisions on the scores primarily, along with other clinical factors. The percentages of physicians influenced by each factor and the totals for each category of treatment will be presented in the final poster.

Conclusions

Oncologists in a large practice are influenced in making breast cancer adjuvant therapy decisons by recent trial data, as well as clinical factors, and may extrapolate from one molecular profile to another. Adjuvant chemo use in HR+ node- patients is likely to remained confined to patients with a high-risk profile, regardless of the assay used.

Legal entity responsible for the study

Florida Cancer Specialists.

Funding

Has not received any funding.

Disclosure

L.L. Hart: Advisory / Consultancy, Travel / Accommodation / Expenses: Self. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

203P - Management of early breast cancer in women over 90: A 10 year experience (ID 818)

Presentation Number
203P
Lecture Time
12:00 - 12:00
Speakers
  • Emily Coffey (Manchester, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The incidence of breast cancer increases with age with approximately 1800 cases per year in the UK occuring in over 90-year olds. We sought to determine the incidence of new breast cancer diagnoses in this subgroup and examine our practice in the management of these women.

Methods

A retrospective case-note review was performed on 32 patients aged 90 years and over, diagnosed with non-metastatic invasive breast cancer between 2007 and 2017. Clinicopathological data was collected on patients’ cancers, co-morbidities, treatment, recurrence and survival.

Results

Median age at diagnosis was 90 years (range 90-99). Median number of comorbidities was 2 (range 0-6). Mean tumour size was 35mm (range 5-85). 11 cancers (34%) were ER negative and 2 (6%) HER2 positive. 12 cancers (38%) were grade 3 at presentation and 12 had positive axillary lymph node metastases. Twenty-seven (84%) patients underwent a mastectomy, including one bilateral, and five (16%) patients had wide local excision. No patients suffered significant complications in the immediate post-operative period. Twenty-one patients (66%) had adjuvant radiotherapy. No patients underwent adjuvant chemotherapy. Eight patients (25%) developed local or distant recurrence and twenty-one patients (66%) died by the end of the study collection period. Mean disease free survival was 46.4 months (95% CI 31.1-61.7 months) and mean overall survival was 45 months (95% CI 31.7-59.7 months).

Conclusions

Optimal management for older patients is achieved by the co-evaluation of the life expectancy, co-morbidities, and the treatment benefit/risk ratio. Our data suggests that treating older patients with focused surgical and adjuvant treatment is appropriate, however further age-adjusted data is required to standardise care in this subgroup.

Legal entity responsible for the study

Pennine Acute Hospitals NHS Trust.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

204P - Evolution in the risk of adverse events of adjuvant endocrine therapy in postmenopausal women with early-stage breast cancer (ID 1141)

Presentation Number
204P
Lecture Time
12:00 - 12:00
Speakers
  • Daniel J. Reinhorn (Petach Tikva, Israel)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Adjuvant endocrine therapy is a gold standard in early-stage, hormone receptor-positive breast cancer. In postmenopausal women aromatase inhibitors (AIs) are associated with improved outcome compared to tamoxifen monotherapy. Differences in the toxicity profiles of these drugs are described, however, little is known about whether the risk of adverse events changes over time.

Methods

Sequential reports of large, randomized, adjuvant endocrine therapy trials comparing AIs to tamoxifen were reviewed. Data on pre-specified adverse events were extracted including cardiovascular events, bone fractures, cerebrovascular disease, endometrial cancer, other secondary malignancies, venous thrombosis and death without recurrence. Odds ratios (ORs) were calculated for serial publications over follow-up. The change in the ORs for adverse events over time was evaluated using weighted linear regression.

Results

Analysis included 22 reports of 7 trials reporting outcomes between 25.8 and 120 months of follow-up. Over time, the differences in toxicity profiles between AIs and tamoxifen did not change significantly (Table). Compared to tamoxifen, longer duration of AI use was associated with a non-significant reduction in the OR for bone fracture and a non-significant increase in the OR for thromboembolic events.

204P

Eventβp
Fractures-0.4310.084
Cardiovascular events-0.1890.557
Cerebrovascular disease0.0880.823
Thromboembolic events0.3890.169
Secondary cancer0.2270.365
Endometrial cancer-0.1040.671
Death without recurrence0.0430.852

Conclusions

Differences in toxicity profiles between adjuvant AIs and tamoxifen do not change significantly over time. Drug-specific toxicity (e.g. bone fractures with AI and thromboembolism with tamoxifen) may fall over time and after discontinuation of treatment.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Amir: Speaker Bureau / Expert testimony: Genentech/Roche; Advisory / Consultancy: Apobiologix; Advisory / Consultancy: Agendia; Advisory / Consultancy: Myriad Genetics. H. Goldvaser: Honoraria (self): Roche. R. Yerushalmi: Honoraria (self): Roche; Honoraria (self): Medison; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Teva. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

205P - Hepatitis B screening and incidence of flare among non-metastatic breast cancer patients treated with anthracyclines (ID 2277)

Presentation Number
205P
Lecture Time
12:00 - 12:00
Speakers
  • Zewen Zhang (Singapore, Singapore)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Singapore has a relative higher prevalence of Hepatitis B carriage at 3.6%. The risk of Hepatitis B virus (HBV) flare which is increased in patients receiving anthracycline chemotherapy has clinical relevance due to associated morbidity. Guidelines recommend a risk-adaptive screening strategy. This study aims to analyze the practice of HBV screening, and incidence of flare among non-metastatic breast cancer patients treated with anthracyclines.

Methods

This is a retrospective review of all non-metastatic breast cancer in the Joint Breast Cancer Registry (JBCR) treated with (neo)adjuvant doxorubicin based therapy between August 2015 and December 2016, across 3 tertiary institutions in Singapore. We examined data collected prior to chemotherapy initiation regarding HBV status, including liver function (LFT), HBV surface antigen (HBsAg), antibody to HBV (Anti HBs), HBV core total antibody (Anti HBc) and HBV deoxyribonucleic levels (HBV DNA). We reviewed the course of HBV carriers (HBsAg positive) or prior HBV exposed patients (Anti HBc total positive and HBsAg negative) during chemotherapy for any HBV flare (abrupt rise of alanine aminotransferase levels to more than 5 times upper limit of normal in a carrier).

Results

492 early breast cancer patients were examined. 484 (98.3%) had HBsAg, 159 (32.3%) had Anti HBs and 16 (3.3%) had Anti HBc performed prior to starting chemotherapy. There were 12 HBV carriers and 4 with previous HBV exposure. Among the 12 HBV carriers, 4 were on antivirals prior to the diagnosis of breast cancer, and 8 were started on antivirals following diagnosis. 1 patient received doxorubicin prior to starting antivirals and developed HBV flare after the first cycle. The patient was started on entecavir, with improvement in HBV DNA levels and LFT, and chemotherapy was resumed. Remaining carriers did not develop flares. The patients with prior HBV exposure were monitored with serial LFT, and did not develop transaminitis.

Conclusions

Patients are almost universally screened for HBV with HBsAg prior to anthracyclines. Our data was consistent with local carriage rate. The incidence of flare is low with appropriate antiviral prophylaxis. HBsAg alone may be sufficient for screening.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

206P - Effect of denosumab on low bone mineral density in postmenopausal Japanese early breast cancer patients receiving aromatase nhibitors: 36-month results (ID 2781)

Presentation Number
206P
Lecture Time
12:00 - 12:00
Speakers
  • Koichi Sakaguchi (Kyoto, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Aromatase inhibitors (AI) are standard as postoperative adjuvant therapy for hormone positive postmenopausal breast cancer. In recent years, the administration period tends to be longer, and bone loss which is a side effect has become a serious problem. We have already reported the effect of denosumab up to 24 months on postmenopausal early breast cancer patients with low bone mineral density (BMD) receiving AIs as adjuvant hormonal therapy. BMD in the lumber spine was found to increase, and the combination of denosumab revealed useful for blocking bone mineral loss in Japanese women receiving AIs.

Methods

Study design: A non-randomized, prospective study at three institutions was conducted in Japan. Patients administered 60 mg of denosumab subcutaneously every 6 months. The BMD of the lumbar spine and bilateral femoral neck was measured at baseline and at 6, 12, 18, 24, 30 and 36 months. The levels of serum tartrate-resistant acid phosphatase isoform 5b (TRAP5b), bone alkaline phosphatase (BAP), albumin-corrected serum calcium concentration was measured at baseline and 1, 6, 12, 18, 24, 30 and 36 months. Patients: Postmenopausal women with early-stage hormone receptor-positive invasive breast cancer who were scheduled to receive an AI as adjuvant hormonal therapy or receiving AI adjuvant therapy were included in the analysis. We also included those who had completed a chemotherapy regimen ≥ 4 weeks before entering the study and patients with low BMD (lumbar spine, right femoral neck, and left femoral neck BMD: -2.5< T-score <-1.0). Endpoints: The primary endpoint was the change in percentage of the BMD of the lumbar spine (L1–L4) from baseline to 12 months.

Results

A total of 103 patients were enrolled. Seventy-three patients completed the study. At 36 months, the BMD of the lumbar spine increased by 8.8%. The BMD of the right and left femoral neck increased by 4.4% and 2.7%, respectively. Symptomatic clinical fractures did not occur in patients receiving AI and denosumab.

Conclusions

At 36 months, as with the data to the previous 24 months, in combination of denosumab for Japanese women receiving adjuvant AI treatment, an increase in BMD was noted.

Clinical trial identification

UMIN-CTR, UMIN 000016173.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Taguchi: Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Daiichi Sankyo Co., Ltd.; Research grant / Funding (institution): Eisai Co. Ltd. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

207P - Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL study (ID 3034)

Presentation Number
207P
Lecture Time
12:00 - 12:00
Speakers
  • Maria Agnese Fabbri (Rome, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

In HER2+ breast cancer (BC) patients (pts) the pathological complete response (pCR) is associated with improved survival. With regimens based on the combination of trastuzumab (T), pertuzumab (P) and chemotherapy, pCR rates are slightly over 48%. We conducted a retrospective analysis on HER2+ BC pts to describe the outcomes of neoadjuvant combination of P+T and chemotherapy in the real-life setting.

Methods

Our cohort included 64 pts treated between Sept 2015 and Mar 2018 in 15 Italian Cancer Centers. Treatment outcomes were analyzed in terms of pCR (defined as ypT0/Tis, ypN0i-) and toxicities, recorded according to National Cancer Institute Common Toxicity Criteria. Statistical analysis was performed with T di Student test and χ2 test.

Results

Overall, in the 55 evaluable pts median age was 50 (range 28-77) and 29 pts (53%) were pre-menopausal. 24 pts (45%) were ER-/PgR-, 12 (21%) ER+/PgR-, 16 (29%) ER+/PgR+, median ki67 was 40. 9% of pts were cT1, 73% cT2, 13% cT3 and 5% cT4; 42 pts (76%) were cN+. All pts received 4 cycles of T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) and P (loading dose 840 mg, followed by 420 mg every 3 weeks). In 42 pts T+P were administered with docetaxel (75 mg/mq every 3 weeks), in 8 pts with paclitaxel (80 mg/mq) and 5 pts received docetaxel and carboplatin (AUC5). In 13 pts also 3 cycles of anthracyclines, according to the FEC scheme, were administered. A pCR was achieved in 29 pts (53%). No significant associations were found between pCR and baseline characteristics or treatments schedule. Seven out of 55 (13%) pts reported G3-G4 toxicities (5 pts neutropenia G3-G4, 1 pt vomiting G3, 1 pt diarrhoea G3, 1 pt anemia G3). Three out of 4 pts treated with docetaxel, carboplatin and P+T reported G3/G4 toxicities. A significant association was found between chemotherapy schedule and toxicities (p = 0.004).

Conclusions

The association of P+T+chemotherapy improved pCR rate in HER2+ BC pts treated in the real-life setting. Our results showed that the selection of chemotherapy that will be associated with the dual blockade of HER2 is of paramount importance in order to avoid severe toxicities and increase the compliance with treatment.

Legal entity responsible for the study

Department of Oncology, Belcolle Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

208P - Real-world comparison of the impact of adjuvant capecitabine in women with high-risk triple-negative breast cancer after neoadjuvant chemotherapy (ID 4772)

Presentation Number
208P
Lecture Time
12:00 - 12:00
Speakers
  • Maysa T. Vilbert (Sao Paulo, Brazil)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Adjuvant capecitabine (adjC) is recommended for patients with triple-negative breast cancer (TNBC) and poor response to neoadjuvant chemotherapy. Despite evidence of benefit, this therapy is not available in situations of limited resources, such as in the Brazilian public health system.

Methods

A retrospective observational cohort study was conducted in Princess Margaret (PM) Cancer Centre in Toronto, Canada, and in A.C.Camargo Cancer Center (AC) in São Paulo, Brazil. Patients with TNBC who had completed neoadjuvant chemotherapy (taxane and/or anthracycline) followed by surgery, with a high residual cancer burden (RCB-II or RCB-III) and received at least 1 cycle of adjC in PM or had active surveillance (AS) in AC were evaluated. A descriptive comparison was made between PM and AC. Recurrence free survival (RFS), overall survival (OS), and safety profile were explored descriptively. Chi-Square test and Mann-Whitney test were used to assess categorical and continuous variables data, while Kaplan-Meier survival and Cox-regression were used for time-to-event analyses.

Results

From 06/17 to 03/19, 21 patients received adjC in PM and from 04/02 to 03/19, 70 patients had AS in AC. Starting dose of capecitabine was 1000 mg/m² bid. Seven patients (43.8%) completed 8 cycles, two (12.5%) received 6 cycles and for the remaining patients therapy is ongoing. The median follow-up was 23 months (range 1.9-36 months). At PM 76.2% of the patients were free from recurrence or death and 81% were alive at 3 years. The mean RFS was better in the adjC group (mean 30.8 months vs 20.0 months HR: 0.23; p = 0.045). Mean OS was 29 months in adjC group vs 28 months in AS (HR: 1.48; p = 0.610). Common adverse events were hand-foot syndrome, fatigue, diarrhea, nausea and anemia. Dose reduction, delay to next chemotherapy cycle or discontinuance of treatment were necessary in 13 (61.9%) patients.

Conclusions

Outcome of patients receiving adjC at PM was better than those on AS in AC, suggesting benefit from this treatment in a real-world setting. AdjC is an inexpensive, widely available and well tolerated oral chemotherapy and should be considered an option for improvement of care even in public health systems of less developed countries.

Legal entity responsible for the study

The authors.

Funding

This work has been supported by a UICC Technical Fellowship.

Disclosure

E. Amir: Speaker Bureau / Expert testimony: Genentech/Roche; Advisory / Consultancy: Apobiologix; Advisory / Consultancy: Agendia; Advisory / Consultancy: Myriad Genetics. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

209P - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals (ID 5627)

Presentation Number
209P
Lecture Time
12:00 - 12:00
Speakers
  • Sabela Recalde (Hospitalet de Llobregat, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Benefit derived from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients (pt) with hormone-receptor–positive HER2 negative early breast cancer. The 21-gene recurrence-score (RS) assay Oncotype DX, provide prognostic and predictive information. Results of the TAYLORx study have confirmed that most of patients with negative node status and RS > 25 can avoid CT without increasing their risk of relapse. However, pt < 50 years (y) and RS > 20 showed benefit with CT.

Methods

Aim: To analyse the impact of age using RS test to change the indication of adjuvant CT and the relationship between different clinical pathological factors and the RS value. We analysed 240 cases out of 251 RS test performed in the 3 ICO Centers during 2017-2018. We compared the adjuvant treatment initially planned according to institutional protocol with the treatment given after RS in the total cohort and in pt < 50 y. We performed a logistical regression analysis of pathological factors and RS.

Results

CT was indicated in all pt before knowing the RS results. Only 46 pt (19%) received CT after RS results. 14 out of 88 pt < 50 y received adjuvant CT (15%). 15 pt <50 y had a RS between 21-25, only 5 of them received CT, because in most of them, the RS was performed prior TAILORx results were published. Nowadays, all of these 15 pt would had received CT: 61/240 (25%). Clinical-pathological characteristics of the series are summarized in the Table. Of the risk factors analysed, only Ki67>25 (<0.001) and PR ≤ 20% (0.01) showed a statistically significant relationship with a higher probability of RS > 25 in a multivariate analysis.

209P

Age median (range)53 (19-76) <50 y 35.1% ≥50 y 64.9%
Tumor size median15 mm
Histological gradeG1 23% G2 69.7% G3 4.4%
Progesterone receptor≤20% 21% >20% 78%
Ki67 median (p25-75)20 (13,28) ≤14 27% 14-25 41% >25% 31%
Nodal status

pN0 57%

pN1mic 15%

pN1a 27%

Conclusions

82% of pt of our series could avoid CT, however this proportion change after TAYLORx results in younger patients. Today 75% of these pt would had avoided CT. Ki67 > 25% and Progesterone Receptor ≤20% were the only pathological factors associated with an increased risk of RS > 25.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

210P - Impact of delayed neoadjuvant systemic chemotherapy on survival among breast cancer patients (ID 3917)

Presentation Number
210P
Lecture Time
12:00 - 12:00
Speakers
  • Mariana Chavez Mac Gregor (Houston, TX, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Delays in the initiation of therapy among patients with early stage and locally advanced breast cancer (BC), can negatively impact survival. Patients treated with neoadjuvant systemic chemotherapy (NSC) usually display tumors with high-risk features. Considering these high-risk characteristics, and the evidence supporting adverse outcomes associated with delays in adjuvant chemotherapy initiation, we sought to determine whether time to NSC is associated with survival outcomes.

Methods

We identified patients diagnosed with invasive primary BC (stage I–III)be tween January 1995-December 2015. All patients were treated with NSC at MD Anderson Cancer Center. Patients were categorized according to their time from BC diagnosis to NSC (in days) into one of the three subgroups: 0-30, 31–60, and 61 days. Primary endpoint was overall survival (OS). Descriptive statistics and Cox Proportional Hazard models were used.

Results

A total of5,137 patients were included. Median follow-up was 6.9 years. The 5-year OS estimates according to time to NSC were 87%, 85% and 83% in patients who received NSC within 0-30, 31-60 and 61 days after diagnosis, respectively (P = 0.006). In multivariable analysis, compared to time to NSC of 0-30 days, delayed NSC 61 days was associated with an increased risk of death (31-60 days HR = 1.05 [95%CI 0.92-1.19]; >61 days, HR = 1.28 [95%CI 1.06-1.54]). In stratified analyses, the association between delay in NSC initiation and increased risk of death was statistically significant for patients with stage I, II (31-60 days: HR = 1.22 [95%CI 1.02-1.47]; 61 days, HR = 1.41 [95%CI 1.07-1.86]) BC and among patients with HER2+ tumors (61 days, HR=1.86 [95%CI 1.21-2.86]).

Conclusions

A delay in NSC initiation of more than 61 days after BC diagnosis is associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus in coordination of care and patient-centered timely treatment planning and delivery.

Legal entity responsible for the study

The authors.

Funding

MD Anderson Cancer Center, Susan G Komen.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

211P - Clinical confirmation of higher exposure to niraparib in tumour vs plasma in patients with breast cancer (ID 2246)

Presentation Number
211P
Lecture Time
12:00 - 12:00
Speakers
  • Laura Spring (Boston, MA, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Niraparib is a selective oral poly(ADP-ribose) polymerase 1/2 inhibitor (PARPi) approved as maintenance treatment of recurrent ovarian cancer. Previous studies revealed unique pharmacological properties of niraparib, including a large volume of distribution, suggesting higher tissue penetration of this drug. Preclinical studies have consistently demonstrated that niraparib tumor exposure is higher than plasma exposure, whereas another PARPi, olaparib, has demonstrated lower tumor exposure than plasma exposure in tumor xenograft models. In a clinical study, tumor concentrations of olaparib were on average 41% of plasma concentrations in patients with breast cancer (BC)1. Here we report for the first time the intra-tumoral concentration of niraparib in clinical samples.

Methods

Tumor biopsies and plasma samples were collected from patients enrolled in a pilot study (NCT03329937) evaluating the antitumor activity and safety of niraparib as neoadjuvant treatment for HER2-negative, BRCA-mutated localized BC. Patients (N = 9) received oral niraparib 200 mg once daily over two 28-day cycles; 2 patients in the analysis had dose reduction to 100 mg. Biopsies and plasma were obtained at the end of Cycle 2. Additional plasma samples were collected on Cycle 2/Day 1 at 0, 2, and 4 hours post dose to determine steady-state maximum concentration (Cmax). Niraparib concentrations in plasma and tumor samples for each patient were quantified using a qualified liquid chromatography–tandem mass spectrometry method.

Results

Niraparib concentrations in plasma from patients with BC (N = 5) were within the reference range previously reported for solid tumors (steady state Cmax 3160+/-2799 nM, Ctrough 1753+/-1707 nM). In the same cohort of BC patients, niraparib concentrations in tumors ranged from approximately 4–131-fold higher than those in corresponding plasma samples after 2 months of niraparib treatment. Data for all patients will be presented at the meeting.

Conclusions

These results provide the first clinical data of at least 4-fold higher intra-tumor concentration of niraparib compared with plasma concentration in patients with BC. Reference: Bundred N et al. Invest New Drugs 2013; 31: 949-58.

Clinical trial identification

NCT03329937.

Legal entity responsible for the study

Tesaro: A Gsk Company.

Funding

Tesaro: A Gsk Company.

Disclosure

M. Shan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro: A GSK Company. E. Hamilton: Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Genzyme; Travel / Accommodation / Expenses: Helsinn Therapeutics; Travel / Accommodation / Expenses: HERON; Travel / Accommodation / Expenses: Lexicon; Travel / Accommodation / Expenses: Medivation; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Sysmex; Travel / Accommodation / Expenses: Guardant Health; Travel / Accommodation / Expenses: Foundation Medicine. C. Santa-Maria: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Medimmune. S. Isakoff: Advisory / Consultancy, Research grant / Funding (institution): Abbvie; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck; Research grant / Funding (institution): OncoPep; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar. D.B. Page: Honoraria (self): Novartis; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nektar; Research grant / Funding (self): NanoString Technologies; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Research grant / Funding (institution): Merck; Speaker Bureau / Expert testimony: Philips Healthcare. P. Pan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro: A GSK Company. K. Sun: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro: A GSK Company. J.R. Graham: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro: A GSK Company. H.S. Han: Research grant / Funding (institution): Tesaro, Inc.; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Prescient; Research grant / Funding (institution): Horizon; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): TapImmune; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Department of Defense. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

212P - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index (ID 581)

Presentation Number
212P
Lecture Time
12:00 - 12:00
Speakers
  • Mohammad I. Hojouj (Dnipro, Ukraine)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer in the world in general and in Ukraine is steadily increasing. Epidemiological, experimental and clinical studies have shown that metabolic disturbances associated with BMI> 30 kg / m2 increase the risk of occurrence and worsen the clinical course of breast cancer. Thus, in patients with obesity, a decrease in the sensitivity of the tumor to systemic antitumor therapy, an increase in the frequency of postoperative complications and a decrease in the rates of general and non-recurrent survival.

Methods

The aim of the study was to improve the results of neoadjuvant systemic antitumor therapy in breast cancer patients with abdominal obesity (BMI greater than 30 kg / m2) by administering levocarnitine in combination with neoadjuvant systemic anticancer therapy (NSAT) for the correction of metabolic disorders as the main pathogenetic part of obesity. Following randomization of all patients (n = 108) with breast cancer with BMI> 30 kg / m2, depending on the appointment of levocarnitine during NSAT, were divided into 2 groups: comparison and observation. In the comparison group, patients (n = 58) with BMI> 30 kg / m2 patients with breast cancer who did not receive levocarnitine during NSPT, and in the, observation group - patients (n = 50) on breast cancer with BMI> 30 kg / m2 who received levocarnitine during NIST

Results

After neoadjuvant systemic anticancer therapy, regardless of the purpose levocarnitine decreased residual tumor cell proliferation index (Ki-67) and increased incidence of Luminal A molecular type of breast cancer. Against neoadjuvant systemic anticancer therapy for breast cancer patients with a BMI over 30 kg / m2 to be additionally administered drugs that increases the incidence of complete morphological regression. This drug is levocarnitine in therapeutic doses (1500 mg / day), which has proven to be an effective means to increase the number of cases of clinically relevant responses (CR + PR) to the treatment.

Conclusions

Levocarnitine contributes to an increase in the number of cases of objective clinical (complete regression and partial regression) and morphological (therapeutic pathomorphosis IV and V degree) tumor response to cytotoxic breast cancer therapy in patients with BMI> 30 kg / m2 and frequency of organ-saving surgical interventions.

Legal entity responsible for the study

The author.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.

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Poster Display session 2 Poster Display session

213P - Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes (ID 5327)

Presentation Number
213P
Lecture Time
12:00 - 12:00
Speakers
  • Silvia Mihaela Ilie (Bucharest, Sec. 2, Romania)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Pathologic complete response (pCR) is a surrogate marker of a better relapse-free (RFS) and overall survival (OS), particularly in HER2 overexpressing and triple-negative breast cancer (TNBC) subtypes. Our aim is to assess the impact of HER2 expression level on pCR, in patients with luminal or TNBC treated with neoadjuvant chemotherapy (NAC).

Methods

We conducted a retrospective analysis in luminal and TN non-metastatic breast cancer patients, addressed to cancer center Georges François Leclerc in Dijon for NAC. Hormone receptor and HER2 expression were centrally assessed according to CAP/ASCO criteria. The pathologic response was dichotomized in pCR and non-pCR and evaluated according to Chevalier classification.

Results

Between 2007 and 2018, 761 patients (pts) were recorded, of which 263 (34.5%) had TNBC and 498 (65.5%) luminal-HER2 negative BC. Among TNBC, 189 pts (70.8%), 54 pts (20.2%) and 24 pts (8.9%) had respectively score 0, 1 and 2, and negative FISH. In luminal tumors these results were respectively 246 (49.3%), 181 (36.3%) and 21 (4.2%). Median age, size of primary tumour and lymph node involvement were similar in both subpopulations. Regarding NAC, 20.9% received only taxanes, 22.1% only anthracyclines and 55.1% both agents. The combination was more often recommended in TNBC 74.2% vs 59.3% (p = 0.03). pCR rate in the primary tumour and lymph nodes was 29% (157 pts) in the whole cohort. This rate varied according to HER2 expression (0, 1+, 2+) from respectively 48.6% (51pts), 36.4% (8pts) and 28.6% (4pts) (p = 0.256) in TNBC and from 8.5% (7pts), 5.3% (5pts) and 4.1% (2pts) (p = 0.532) among luminal tumors. Both OS and RFS were associated with a good Chevalier pathologic response (p < 0.001) in TNBC but not in luminal tumours (p = 0.5257 and p = 0.9845). Neither pCR, nor the Chevalier response was statistically correlated with HER2 score.

Conclusions

No correlation between pCR and the level of HER 2 expression was found neither in luminal nor in TNBC patients. In TNBC patients, differences in terms of pCR were noticed between the 3 HER expression groups. The predictive role of HER2 expression should be further explored in early localized TNBC in a larger population.

Editorial acknowledgement

Isabel Gregoire, medical writer, Department of Biostatistics Georges Francois Leclerc Cancer Center, Dijon, France.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

214P - Pre-specified interim analysis of the SAFE trial (NCT2236806): A 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab (ID 3613)

Presentation Number
214P
Lecture Time
12:00 - 12:00
Speakers
  • Lorenzo Livi (Firenze, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

SAFE trial (NCT2236806) is a phase 3 study comparing the effect on subclinical heart damage of bisoprolol (B), ramipril (R), or both drugs (R+B), as compared to placebo (P), in breast cancer treated with (neo)adjuvant anthracyclines +/- trastuzumab.

Methods

Primary endpoint is subclinical cardiotoxicity measured with echocardiography and global linear strain (GLS). This interim analysis was pre-specified on the first 120 patients who had completed cardiological assessments at 12-mos. Stopping rules per arm were: dose reduction >15%, study withdraw rate >5%, and no significant impact on 3D-left ventricular ejection fraction (3D-LVEF) as compared to T0 at 12-mos assessment.

Results

A total of 191 out of 480 patients have been enrolled; overall 123 patients were available for the analysis (P = 34; R = 28; B = 31; R+B=30). 3D-LVEF decreased at 3-mos (-3.3%; p < 0.001), at 6-mos (-5.2%; p < 0.001) and at 12-mos (-3.7%; p = 0.004) respect to T0 in P; at 3-mos (-2.4%; p = 0.001), at 6-mos (-1.9%; p = 0.010), at 12-mos (-2.2%; p = 0.045) in R. In B and R+B patients no significant changes were observed at 3- and 12-mos, with a decrease at 6-mos (-2.5% and 3.0%, respectively; p = 0.002). Arm differences were significant (p = 0.038). GLS increased at 3-mos (5.7%; p < 0.001), at 6-mos (7.8%; p < 0.001) and at 12-mos (7.1%; p < 0.001) respect to T0 in P; at 3-mos (2.7%; p = 0.002), at 6-mos (3.2%; p = 0.014), but not at 12-mos in R; no significant changes at 3-mos, a significant increase at 6-mos (2.7%; p = 0.035), at 12-mos (3.2%; p = 0.008) in B; no significant changes at 3-, 6-, and 12-mos in R+B. Arm differences were significant (p = 0.002). Both R+B and the R arms showed a withdraw rate of 7%, with a dose reduction rates of 21% and 17%, respectively. R arm showed a significant decrease on 3D-LVEF at 12-mos as compared to T0 and will be evaluate for closure.

Conclusions

Following the stopping rules, the closure of the R arm is required and the study will continue with 3 arms. At the interim analysis, a cardioprevention strategy significantly impact on subclinical heart damage.

Clinical trial identification

NCT2236806.

Legal entity responsible for the study

University of Florence.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

215P - Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: A multi-center comparative study (ID 3736)

Presentation Number
215P
Lecture Time
12:00 - 12:00
Speakers
  • Icro Meattini (Firenze, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

For decades, conventionally fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase 3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients (<60 years) are not currently worldwide treated with HF-WBI. The aim of this multi-center comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.

Methods

Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centers: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24, and 36 months.

Results

At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute edema (p = 0.0001), acute wet desquamation (p = 0.009), chronic edema (p = 0.0001), chronic erythema/pigmentation (p = 0.0001), and breast fibrosis (p = 0.0002). At multivariate logistic analysis, hypofractionation was independent significant factor for acute edema (OR 0.09, 95% CI 0.02 to 0.48; p = 0.005), acute wet desquamation (OR 0.07, 95% CI 0.009 to 0.59; p = 0.014), and chronic edema (OR 0.18, 95% CI 0.04 to 0.75; p = 0.018). Significant association between individual characteristics and toxicity (grade 2 or more) are summarized in Table.

215P

ToxicityNProtective factorp-valueOR (95%CI)Risk factorp-valueOR (95%CI)
Acute edema43Hypofractionation Dmax/Prescribed dose° <107%0.0001 0.0010.09 (0.03-0.30) 0.16 (0.06-0.46)Chemotherapy0.0022.63 (1.42-4.90)
Chronic edema50Hypofractionation Dmax/Prescribed dose° <107%0.0001 0.0030.20 (0.09-0.44) 0.31 (0.14-0.66)EIC presence Boost dose >10 Gy Breast size >492 cc0.0001 0.032 0.0033.0 (1.66-5.46) 9.02 (1.21-67.45) 2.67 (1.41-5.05)
Acute erythema/ pigmentation163HER2 positive status Trastuzumab0.002 0.0220.30 (0.14-0.63) 0.39 (0.18-0.87)Smoking habits Boost dose >10 Gy Breast size >492 cc0.001 0.038 0.0022.14 (1.37-3.32) 2.60 (1.06-6.41) 1.78 (1.24-2.54)
Chronic erythema/ pigmentation110Hypofractionation Dmax/Prescribed dose° <107%0.0001 0.0010.40 (0.25-0.63) 0.45 (0.28-0.73)EIC presence Positive FSM Boost dose >10 Gy Breast size >492 cc0.0001 0.002 0.007 0.0342.39 (1.54-3.71) 3.47 (1.56-7.71) 15.43 (2.08-114.3) 1.58 (1.04-2.41)
Acute wet desquamation20Hypofractionation Dmax/Prescribed dose° <107%0.009 0.0470.14 (0.03-0.61) 0.29 (0.08-0.99)---
Breast fibrosis117Hypofractionation Tumor grade Ki67 index Dmax/Prescribed dose° <107%0.0002 0.022 0.023 0.0170.44 (0.29-0.68) 0.53 (0.31-0.92) 0.60 (0.38-0.93) 0.58 (0.37-0.91)EIC presence Boost dose >10 Gy Breast size >492 cc0.0001 0.022 0.00013.03 (1.99-4.62) 6.76 (2.04-22.45) 2.84 (1.83-4.41)

Conclusions

HF-WBI showed significantly improved toxicity outcomes in terms of both acute skin edema and wet desquamation, and chronic skin edema. HF-WBI after BCS should replace CF-WBI independently of age.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

216P - Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab (ID 5085)

Presentation Number
216P
Lecture Time
12:00 - 12:00
Speakers
  • Isabel Blancas López-Barajas (Granada, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Trastuzumab is a highly efficient drug in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority, especially in the presence of comorbidities. Left ventricle ejection fraction (LVEF) determination remains the most used technique to diagnose cardiotoxicity in clinical practice. The purpose of this study is to analyse the usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab.

Methods

The study included 66 patients who received trastuzumab. We collected the LVEF and NT-proBNP values measured during the course of treatment, and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and BMI. Cardiotoxicity was diagnosed during the follow-up program considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. According to the literature, NT-proBNP cut-off points were considered to stablish normal or abnormal values in terms of patent age.

Results

174 paired LVEF/NT-proBNP values were found. 27.3% of patients suffered cardiotoxicity during trastuzumab treatment and most of cases were diagnosed based on cardiac symptomatology (66.7 %). Logistic regression analysis of NT-proBNP and the cardiovascular risk factors showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2 - 28.5, p = 0.028) and NT-proBNP (OR 22.0, 95% CI 5.7 - 85.4, p = 0.000) with the development of cardiotoxicity during trastuzumab treatment, whereas the other variables were not statistically significant.

Conclusions

Diabetes and NT-proBNP values seem to be associated with an increased risk of cardiotoxicity in breast cancer patients during trastuzumab treatment. In diabetics, glycaemic control and a more intense cardiac monitoring could provide objective benefits during the treatment. Moreover, NT-proBNP determination could become an accessible way to evaluate cardiac risk in this context.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

217P - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified (ID 5747)

Presentation Number
217P
Lecture Time
12:00 - 12:00
Speakers
  • Fanny Preat (Brussels, Belgium)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The use of sentinel lymph node biopsy (SLNB) during breast surgery for ductal carcinoma in situ (DCIS) is controversial. It is accepted in high risk lesions (high histological grade, palpable, large >25 mm, and multifocal lesions) since it avoids a second operation if the definitive diagnosis reveals infiltrating ductal carcinoma (IDC) and its recommended due to some technical obligations in patients with planned total mastectomy or with tumor localization to the upper outer quadrant.. We aimed to evaluate the use of SLNB in patients with preoperative diagnosis of high risk DCIS lesions.

Methods

A monocentric retrospective study was conducted on 467 patients with primary diagnosed DCIS operated for partial or total mastectomy with or without SLNB. The frequency of each risk factor, and the incidence of IDC were calculated in the overall series. The predictive value of each risk factor is calculated by comparing these factors in the groups depending to the definitive pathology (IDC vs DCIS) using the chi square test. A value of p < 0.05 was considered significant.

Results

Breast surgery was done within a median of 42 ± 23 days of DCIS diagnosis. Median age was 57± 10 years. High risk DCIS lesions accounted for 73.1% of all cases (342/468). Grade III lesion, multifocal, palpable and larger than 25 mm lesions were present in 263 (56.3%), 61 (13.1%), 86 (18.4%) and 99 (21.2%) respectively. IDC was diagnosed in 95/468 patients (20.3%) in the global series and in 75patients/342 (22%) in the patients with high risk lesions. A palpable lesions and a tumor diameter >25 mm were associated with higher risk of invasive carcinoma (p = 0.007 and p = 0.017 respectively).Overall SLNB was done in 383 patients (82%), of which 318 patients (83%) had high risk lesions. A Positive SLN was detected in overall 5 patients (1.3%), all of which had high risk lesions (5/318: 1.6%).

Conclusions

In our study, the preoperative classification of high risk lesion showed a 79% sensitivity (75/95) and a 22% specificity (75/342) of detecting IDC. A positive SLN was found in only 1.6% of patients with high risk CDIS lesions operated for SLNB. The use of SLNB in patients with high risk DCIS avoids reoperation in 22% of cases. Nevertheless the low risk of positive SLN finding in this setting cannot justify its routine use.

Legal entity responsible for the study

Jean Marie Nogaret.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

218P - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer (ID 1837)

Presentation Number
218P
Lecture Time
12:00 - 12:00
Speakers
  • Kenjiro Jimbo (Tokyo, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Positive margin of breast-conserving surgery (BCS) is well known to be a risk factor for ipsilateral breast tumor recurrence (IBTR). SSO/ASTRO guidelines defined ink on invasive cancer or DCIS as positive margin and recommend considering doing re-excision of the site of positive margin. However, whether re-excision can reduce IBTR has not been fully investigated yet. The aim of this study was to retrospectively assess the oncological impact of re-excision for positive margin status after BCS in invasive breast cancer.

Methods

The subjects were 196 invasive breast cancer patients who underwent BCS, and who were found to have positive margin. Of the 196 patients, 55 underwent re-excision after initial BCS (group A), and 139 did not (group B). We analyzed IBTR free survival in each group and evaluated the predictors for IBTR and overall survival (OS) using Cox proportional hazards modeling.

Results

Of the 196 patients, 188 (96%) underwent adjuvant radiotherapy and 24 of 55 re-excision (43%) identified residual disease. There was no significant difference in 10-year IBTR free survival between group A and group B (94.4% versus 93.8%; P = 0.58). In a multivariate analysis, re-excision was not associated with IBTR and OS, while younger age, lack of adjuvant radiotherapy, and invasive component of margin status were independent predictors of IBTR.

Conclusions

In our retrospective study, re-excision for positive margin after initial BCS in invasive breast cancer does not contribute to prevent IBTR and may not translate into improved OS. Further treatment should be considered when patient was younger and margin status was invasive component.

Legal entity responsible for the study

Kenjiro Jimbo.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

219P - Pneumonitis and fibrosis after breast cancer radiation (ID 4347)

Presentation Number
219P
Lecture Time
12:00 - 12:00
Speakers
  • Jarle Karlsen (Trondheim, Norway)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer(BC) radiation therapy(RT) reduce local recurrence, BC mortality and improves overall survival, but may induce lung damage ranging from radiological changes only to respiratory failure. Lung toxicity may present as radiation pneumonitis (RP) 3-6 months after treatment and radiation fibrosis (RF) after 6-12 months. The aim of the study is to describe the occurrence of RP and RT after conventional RT and examine their potential predictors.

Methods

250 patients were entered in a prospective cohort study from February 2007 to October2008. All patients received standard postoperative 3D conformal radiation therapy (2 Gy x 25) for BC. Pulmonary High Resolution Computer Tomography and clinical examinations were performed before RT and 3, 6 and 12 months after radiation treatment. Smoking habits were reported by patients. Estimated lung dosevolums (V20, V30, D25) were retrieved from the doseplan system(Oncentra). Patient- and treatment-related factors were registered by oncologists at start. Evaluation of RP and RF were performed by a radiologist according to NC&Iacute;s CTCAE (version 3.0 ). Predictors of RP and RF were evaluated by univariate and multivariable logistic regression. Patient reported outcomes were measured using EORTC QLQ-C30.

Results

The occurence of RP 3 months after radiation therapy was 76.6% and RF 12 months after treatment was 90.5 %. 17.5% had symptomatic RP and 17.1% symptomatic RF, mainly as grade 1. In We identified correlation between mastectomy and symptomatic RP (OR = 2.41 p < 0.05), age and RF (OR = 1.08 p < 0.05) and endocrine treatment and symptomatic RF (OR = 2.24 p < 0.05). Smoking seems to have a protective effect against RP also demonstrated in multivareble analysis (OR = 0.34 p < 0.05). Before radiation treatment 30.3 % of the patients reported dyspnoea, at 3 months 42.7% and at 12 months 39.8%. Physicians registered dyspnoea by 8.4% before treatment, 14.3% at 3 months and 10.4% at 12 months.

Conclusions

Our data shows that RP and RF is common the first year after BC radiation. We identified that age was associated with RP, mastectomy with symptomatic RP and endocrine therapy with symptomatic RF. Dyspnoea were more frequent reported by patients than physicians.

Legal entity responsible for the study

Faculty of Medicine and Health, NTNU, Norway.

Funding

Sentral Norway Regional Health Authority.

Disclosure

The author has declared no conflicts of interest.

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Poster Display session 2 Poster Display session

220P - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: A nationwide study of the Korean Breast Cancer Society (ID 2280)

Presentation Number
220P
Lecture Time
12:00 - 12:00
Speakers
  • Sungmin Park (Cheongju, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

We compared the prognosis of patients with breast cancer according to surgical options including mastectomy with reconstruction after neoadjuvant chemotherapy (NAC). We also assessed the association between prognosis and surgical options according to clinical stage and clinical response in patients with neoadjuvant chemotherapy.

Methods

A total of 140,712 patients were enrolled in the Korean Breast Cancer Society Registry database between 2000 and 2014 in Korea. We compared the prognosis of three groups; 1) patients who underwent breast-conserving surgery (BCS), 2) patients who underwent mastectomy, and 3) patients who underwent mastectomy with reconstruction.

Results

Of all 6,634 patients who were treated with NAC, 1,745 patients underwent BCS, 1,459 patients underwent mastectomy, and 363 patients underwent mastectomy with reconstruction. In survival analysis, five-year survival rate (5YSR) of mastectomy with BR group was not inferior compare to other groups in clinical stage IIA and IIB. 5YSR of mastectomy with BR group was 100% and 90.0% clinical stage IIA and IIB, whereas 5YSR of mastectomy group was 97.2% and 86.2% (clinical stage IIA and IIB; P = 0.033 and 0.023). In clinical stage IIIA and IIIB, there was no significant difference in 5YSR between mastectomy with BR group and other groups. However, women who underwent mastectomy with BR had a worse prognosis compare to BCS or mastectomy group in clinical stage IIIC. In univariate analysis by Cox regression method according to surgical methods, women who underwent mastectomy with BR had a worse prognosis compared to other groups in patients with clinical stage IIIC (HR 5.88; 95% CI 2.17-15.89; P < 0.001). In multivariate analysis, women who underwent mastectomy with reconstruction followed by NAC were associated with a worse prognosis in clinical stage IIIC. (HR 3.41; 95% CI 1.29-8.99; P = 0.013).

Conclusions

In this study, women who underwent mastectomy with reconstruction followed by NAC were associated with a worse prognosis in the clinically advanced stage. This study suggests that reconstruction followed by NAC should be considered for appropriately selected patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

221P - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer (ID 804)

Presentation Number
221P
Lecture Time
12:00 - 12:00
Speakers
  • Chang-ik Yoon (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

A decrease lymphocyte to monocyte ratio (LMR) has been reported to be related with worsen prognosis for certain hematologic and solid malignancies. Also pretreatment LMR is associated with the prognosis of patients with breast cancer. However, relationship between treatment-related low LMR and prognostic impact has not well been investigated in breast cancer. The purpose of this study is to evaluate the relationship between radiotherapy (RT)-induced low LMR and recurrence in patients with breast cancer.

Methods

We retrospectively reviewed 1,735 patients with stage I to III breast cancer treated with breast conserving surgery (BCS) and adjuvant RT at Gangnam Severance Hospital and Severance Hospital from January 2006 to 2016 December. The values of LMR were calculated at baseline (A1), before the first RT administration (A2) and before the last RT administration (A3). The reference point of RT-induced low LMR was defined as ≤ 2.6 used in other studies. The recurrence-free survival (RFS) was compared according to RT-induced LMR.

Results

We retrospectively reviewed 1,735 patients with stage I to III breast cancer treated with breast conserving surgery (BCS) and adjuvant RT at Gangnam Severance Hospital and Severance Hospital from January 2006 to 2016 December. The values of LMR were calculated at baseline (A1), before the first RT administration (A2) and before the last RT administration (A3). The reference point of RT-induced low LMR was defined as ≤ 2.6 used in other studies. The recurrence-free survival (RFS) was compared according to RT-induced LMR.

Conclusions

We demonstrated that RT-induced low LMR is a poor prognostic factor for patients with BCS and adjuvant RT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

223P - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe (ID 2701)

Presentation Number
223P
Lecture Time
12:00 - 12:00
Speakers
  • Francesco Giusti (Ispra, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The basic scope of population-based cancer registries (CRs) is to collect data that enable computation of cancer incidence. In addition to this, nowadays most registries can provide more extensive information such as data on stage and treatment, which could be used to assess and compare different care pathways. The current analysis reports on treatment by stage patterns for female breast cancer in Europe.

Methods

Data from CRs included in the European Cancer Information System (ECIS) and having submitted data on stage and treatment for the ENCR-JRC project were analysed. Proportion of cases by treatment type: surgery (SG), radiotherapy (RT), systemic therapy (ST), by stage, age, period and region were calculated.

Results

829,247 cases from 20 CRs were analysed. Treatment for stage I (UICC TNM) patients aged 19-74 in 1999-2005 was SG alone (22%), SG+ST (13%) SG+RT (31%), SG+RT+ST (32%). SG alone decreased to 18%, while SG+RT+ST rose to 37% in 2006-13. High variability was observed: in Eastern Europe SG alone was 31%, SG+ST 17%, SG+RT 24%, SG+RT+ST 23% in 2006-13, in Western Europe SG alone was 12%, SG+ST 13%, SG+RT 31%, SG+RT+ST 43%. For age 75+ in 1999-2005 SG (37%) and SG+ST (20%) were higher than in 19-74 patients, while SG+RT (17%) and SG+RT+SG (15%) were lower. SG decreased to 31%, SG+RT+ST rose to 20% in 2006-13. Untreated patients were 3% in both periods. For the regional comparison, in 2006-13 SG alone was 50% in Eastern Europe vs 25% in Western Europe; SG+RT+ST was 9% in Eastern Europe, 24% in Western Europe. In 2006-13 for younger stage IV patients SG alone was 7%, ST alone 29%, SG+ST 18%, SG+RT+ST 14%, no treatment 9%. For 75+ patients SG was 11%, ST 30%, SG+ST 12%, SG+RT+ST 7%, no treatment 15%.

Conclusions

Variability in treatment patterns was observed by stage, age, period and region. Clinical information from CRs should be routinely used to monitor clinical care patterns, according to national and international recommendations, to compare levels of compliance and inform policy.

Legal entity responsible for the study

European Commission.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

224P - A critical appraisal of quality indicators of breast cancer treatment in Belgium (ID 1437)

Presentation Number
224P
Lecture Time
12:00 - 12:00
Speakers
  • Didier M. Verhoeven (Brasschaat, Belgium)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

A task force was created by the Belgian Society of Medical Oncology (BSMO) to monitor the quality of treatment of breast cancer in Belgium. In collaboration with the Belgian Cancer Registry an analysis of the data was performed in search of reliable quality indicators. Finding actionable differences can lead to better treatment of our patients.

Methods

Data of 48,872 patients diagnosed with invasive breast cancer between 2010 and 2014 were analysed. To enable risk stratification according to their surrogate subtype, pathology reports of year 2014 were manually checked (9,855 patients). We identified patients < 70 Y (years) and > 75 Y receiving adjuvant radiotherapy after mastectomy and the different systemic treatments in each surrogate subtype. We also calculated the total length of endocrine treatment and the percentage of chemotherapy given in first line ER+ metastatic patients.

Results

In cStage I-III, post-mastectomy radiotherapy was administered in 70.7% of the patients <70 Y and in 46.5% of patients > 75 Y, with an important intercenter variability. 81.7% of the cStage I-III patients <70 Y received at least 4.5 years of adjuvant endocrine therapy, with a slight decrease each year. In the 2014 cohort we identified 54.4% luminal A-like, 14.9% luminal B-like HER2-, 12.4% luminal B-like HER2+, 4.6% non luminal HER2+, 8.6% triple negative and 5.1% unknown. As a negative indicator, 44.6% of the HER2+ pT1aN0 patients <70 Y received adjuvant trastuzumab, compared to 22.2% of the patients > 70 Y. As first treatment for cStage IV HR+/HER2- patients, we identified endocrine therapy in 53.9% and chemotherapy in 17.3%.

Conclusions

Substantial treatment differences were observed among centers. Overtreatment is an important negative quality aspect of breast cancer management. A frequent use of postmastectomy radiotherapy was observed. The use of trastuzumab was inappropriate in pT1aN0 patients. Chemotherapy was used too often in first line hormone receptor positive metastatic patients.

Legal entity responsible for the study

Belgian Cancer Registry.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

225P - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada (ID 1534)

Presentation Number
225P
Lecture Time
12:00 - 12:00
Speakers
  • Phillip Blanchette (London, Canada)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Adjuvant endocrine therapy (AET) is an important treatment for post-menopausal hormone receptor positive breast cancer. We used health administrative data to explore factors associated with AET adherence and survival.

Methods

We used health administrative databases to investigate adherence of post-menopausal women (aged ≥ 66 years) who started endocrine therapy from 2005-2010. Adherence was measured by medical possession ratio (MPR) and characterized as low (<40% MPR), intermediate (40-79% MPR) or high (≥80% MPR) over a five-year period. We investigated factors influencing AET adherence using a multinomial logistic regression model and the association with all-cause death (5-years after starting AET) using a multivariable cox-proportional hazards model.

Results

We identified 5,692 eligible patients with a median age of 73 years (IQR: 69-78), 67% received lumpectomy, 33% mastectomy, 26% adjuvant radiation, 13% adjuvant chemotherapy and 70% of patient originally started on an aromatase inhibitor versus tamoxifen. AET adherence was low in 13% (n = 749), intermediate in 13% (n = 733) and high in 74% (n = 4,210) of patients. Lower levels of adherence were observed among older patients [low vs. high adherence: odds ratio (OR)=1.03, 95% CI: 1.02-1.05 (per year); intermediate vs. high adherence: OR = 1.02, 95% CI: 1.01-1.04 (per year)]. High adherence was associated with use of adjuvant chemotherapy (low versus high adherence OR = 0.42 95% CI: 0.30-0.59) and short-term follow-up with a medical oncologist within 4 months of starting AET (low vs. high adherence OR = 0.83, 95% CI: 0.69-0.99). Unadjusted analysis showed an increased risk of death among patients with lower AET adherence [low vs. high adherence: hazard ratio (HR)=1.31, 95% CI: 1.12-1.53 and intermediate vs. high adherence: HR = 1.40, 95% CI: 1.21-1.62]. However, a significant association could no longer be detected after multivariable adjustment.

Conclusions

Non-adherence to endocrine therapy appears to be more common among older breast cancer patients. Short-term follow-up visit by a patient’s medical oncologist after starting AET may help to improve adherence. Developing strategies to optimize endocrine therapy adherence are warranted.

Legal entity responsible for the study

The authors.

Funding

Academic Medical Association of South Western Ontario (AMOSO).

Disclosure

T. Vandenberg: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche. K. Pritchard: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Myriad Genetics. A. Louie: Advisory / Consultancy: AstraZeneca; Honoraria (self): Varian Medical Systems Inc. J. Raphael: Honoraria (self): Hoffmann La Roche. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

226P - Evaluation of endocrine therapy and patients preferences in early breast cancer: Results of Elena study (ID 4363)

Presentation Number
226P
Lecture Time
12:00 - 12:00
Speakers
  • Emilia Montagna (Milan, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Hormonal therapy (HT) is generally proposed to all patients with endocrine receptor positive breast cancer to reduce the risk of recurrence and death. However, HT is associated with side effects. The aim of the present study was to determine the preferences of women treated with adjuvant HT for breast cancer.

Methods

Preferences have been elicited with a self-completed, validated questionnaire administered at study entry in eligible patients. The questionnaires, showing hypothetical scenarios based on potential survival times (5 or 15 years) and rates (60% or 80% at 5 years) without HT, were used to determine the lowest gains women judged necessary to make the treatment. The analyses were conducted into three different groups of early breast cancer patients to evaluate the expected survival benefit before starting HT (A), after a few months from the beginning (B) and after several years of HT (C). Patients also completed psychological questionnaires and the patient reported symptoms form.

Results

A total of 452 patients were included in the study: 149 in group A, 150 in group B and 153 in group C. In group C, 65% of patients were receiving HT with aromatase inhibitors (with or without a LHRH analogue). 12%, 24% and 35% of patients received adjuvant chemotherapy in group A, B and C, respectively. Overall, 355 women (79%) had children. The responses were quite similar between the three groups. A mean gain of 13 years was judged necessary to make adjuvant endocrine therapy worthwhile based on the hypothetical scenario of untreated mean survival time of 15 years. A mean gain of 22% more women surviving was judged necessary to make adjuvant HT worthwhile based on an untreated 5-year survival rate expectation of 60%. Cognitive dysfunction was considered the side effect least compatible with the continuation of treatment in all three groups. The willingness to continue therapy was unrelated to age, marriage and presence of children.

Conclusions

This is a large study of patient preferences on HT. Preferences have been elicited also in premenopausal patients treated with aromatase inhibitors. Compared with other studies with similar design, the patients included in the present study required larger benefits to make adjuvant therapy worthwhile.

Clinical trial identification

NCT 03939156 Release date 05.03.2019.

Legal entity responsible for the study

The authors.

Funding

Women cancer center.

Disclosure

E. Montagna: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: gentili; Advisory / Consultancy: Novartis. M.A. Colleoni: Honoraria (self): Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex; Advisory / Consultancy: AstraZeneca. G. Cancello: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: gentili. E. Munzone: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Genomic Health. S. Dellapasqua: Travel / Accommodation / Expenses: Roche. M. Mazza: Advisory / Consultancy: Novartis; Advisory / Consultancy: Gentili; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Celgene; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

227P - Baseline quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): The French multicentric prospective CANTO cohort study (ID 2679)

Presentation Number
227P
Lecture Time
12:00 - 12:00
Speakers
  • Idlir Licaj (Caen, France)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

In this study we aimed to examine the independent effect of baseline QoL and persistent CRT among pts with early BC.

Methods

We included data stage I-III BC pts treated with chemotherapy who were included in the CANTO prospective cohort study (NCT-01993498) from 03/2012 to 12/2014. The primary outcome was CRT defined as the presence at 3-6 months after the end of treatment, of any of the following toxicities (NCI-CTC-AE): infection, venous or arterial thrombosis, neurological G2-4, digestive G3-4 or pulmonary toxicities G3-4). Treatment deliver including chemotherapy dose reductions were also examined. The independent variable of this study was baseline Qol defined by the EORTC QLQ-C30 subscales of general global health status (GHS) (< or ≥ 70) and physical functioning PF (< or ≥ 90). The defined cutoffs correspond to the average values in the French general population. Clinical relevant adjustment covariates included stage, age, performance status (PS), body mass index (BMI), HR and HER2 status, baseline lymphopenia, albumin, creatinine clearance, alcohol consumption, and smoking status. Multivariable logistic models were performed.

Results

Among 3079 BC pts included in this analysis, 33% received neoadjuvant and 77% adjuvant treatment. Median age at diagnosis was 53 years, median BMI= 25 kg/m2, 94% of patients had a PS = 0 and 83% stage I-II disease. Pts reported on average a good GHS = 68 (±19) and PF = 90 (±14). GHS and PF were higher in women with better performance status PS = 0 vs 1+, (68 vs 60 p < 0.001) and 91 vs 78 p < 0.001) respectively. 952 (31%) BC pts developed ≥1 CRT: 23% had an infection, 7% thrombosis, 0.3% G3-4 diarrhea, nausea or vomiting, 4% G2-4 neurological and 0.2% G3-4 pulmonary toxicities. 16% had chemotherapy dose reduction. Pts with a baseline GHS <70 had 19 % higher odds of CRT vs to those with GHS≥70, OR = 1.19 [95% CI 1.02-1.41] and similarly those with a PF < 90 had a 23% higher odds of CRT when compared to those with PF ≥ 90 (OR = 1.23 [95% CI 1.03-1.49]).

Conclusions

Global and physical QoL before BC treatments are independently associated with CRT. QoL should be assessed before any treatment to identify patients at risk CRT.

Clinical trial identification

NCT01993498.

Legal entity responsible for the study

UNICANCER/Villejuif, France, 94805 Principal Investigator: Fabrice André Gustave Roussy – Villejuif.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

228P - Effects of aerobic and resistance exercise on android: Gynoid fat ratio in breast cancer survivors (ID 2840)

Presentation Number
228P
Lecture Time
12:00 - 12:00
Speakers
  • Christina Dieli-Conwright (Los Angeles, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The android:gynoid percent fat ratio (AGFR) is associated with increased risk of cardiovascular disease and type 2 diabetes in breast cancer survivors (BCS). Exercise reduces fat mass in BCS; however, few studies have focused on AGFR. The study purpose was to examine the effects of a 16-week aerobic and resistance exercise intervention on AGFR among BCS. We assessed whether exercise-induced changes in AGFR were associated with improved insulin resistance.

Methods

BCS (Stage I-III) were randomized to exercise (n = 50) or usual care (n = 50). The thrice weekly 16-week intervention included supervised, progressive moderate-vigorous aerobic and resistance exercise. AGFR was obtained from a whole-body dual-energy x-ray absorptiometry. Insulin resistance was estimated using homeostatic model assessment of insulin resistance (HOMA-IR) calculated from fasting insulin and glucose levels. Within and between group differences were assessed by paired t-test and repeated measures ANOVA. Pearson’s correlation was computed to assess the association between AGFR and HOMA-IR in the exercise group.

Results

Participants were 53 ± 10.4 years old, overweight (BMI>25.0 kg/m2; 54%), Hispanic (63.1%), and had undergone a mastectomy (90%) and chemotherapy + radiation therapy (76%). Adherence to the intervention was 95% and post-intervention assessments were available on 91% of participants. Post-intervention, AGFR significantly decreased in the exercise group from baseline and when compared to usual care (p < 0.001). Post-intervention, strong correlations were found between AGFR and HOMA-IR (r = 0.95; p < 0.01).

Conclusions

A progressive aerobic and resistance exercise intervention is an effective strategy to decrease AGFR in BCS. BCS who experience exercise-induced improvements in AGFR may also experience improved insulin resistance thereby reducing the risk for comorbid conditions.

Clinical trial identification

NCT01140282.

Legal entity responsible for the study

The authors.

Funding

National Cancer Institute.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

229P - Impact of education for breast self examination in rural Indian women on early detection: Results of POC study (ID 869)

Presentation Number
229P
Lecture Time
12:00 - 12:00
Speakers
  • Sneha S. Parchuri (Hyderabad, India)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer contributes to 19-34% of all malignancies- indicating the high disease burden. In view of various socio-economic and cultural reasons, patients usually present at an advanced stage because of lack of awareness and nonexistent breast cancer screening programs in India. Breast self-examination (BSE) is easy cost effective and proven way for early detection.

Methods

Objective: 1. To train women for Breast self-examination in health camps 2. To determine the effectiveness of planned teaching program with respect to BSE Materials & methods: Trained workers and physician prepared a visual aid and short video in local language for breast self examination and spend average 8-12 minutes to educate a group of women. 15:1 random check was done to known their level of understanding and correctness of adopting the method. The participants were observed and supervised by doctors to complete the procedure successfully. The results of Breast Self-Examination were documented.

Results

BSE was successfully trained for a total of 4965 women across 19 camps between 2018-2019. Out of the samples 93% of women understood accurately the right method of BSE and re-traing was felt necessary in 35% as per their perception. Among the camps 165 new cases were reported in participants. Upon physician’s examination 132 suspected participants were referred for mammographic evaluation at medical centers and malignancies were detected in 76 participants, which indicates high impact of such training programs in rural India.

Conclusions

Conclusion: cancer awareness and education programs should be an integral part of health camps to improve women’s health and BSE Is easy to teach and have positive impact for early detection of cancer (the detection rate of 1.5% was quite high especially in the rural areas where medical facilities are poor). If implemented in structured manner BSE is the best and cheapest option for screening women of all ages in Indian population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

230P - Breast cancer incidence and survival in renal transplant patients: 35-year experience (ID 1951)

Presentation Number
230P
Lecture Time
12:00 - 12:00
Speakers
  • Michalis Kontos (Athens, Greece)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Renal transplantation is known to be associated with increased risk of malignancy. Concurrent presence of malignant diseases and transplantation may influence overall survival. This study summarizes our 35-year experience in breast cancer (BC) in renal transplant patients focusing on the incidence of BC and its impact on survival of this population.

Methods

Prospectively collected data of female patients treated with renal transplantation for chronic renal failure from 1973 to 2017 were analysed. Patients diagnosed with BC were identified. Age at transplantation, age at BC diagnosis, date and causes of death were recorded for all patients. BC incidence and overall survival were calculated. Kaplan-Meier and Cox proportional hazards models were used to determine the difference in survival and hazard between the two patient groups.

Results

Out of 821 transplant patients, 7 developed BC. The mean age in the total population of kidney transplant patients was 42.7 years (SD = 13.8), while the mean age of women diagnosed with BC was 48.3 years (SD = 10.2) and 53.0 years (SD = 12.3), at transplantation and BC diagnosis respectively. In total 7 women (1.0%) were diagnosed with BC of which 4 died from BC and 1 from a different cause. The median survival for women diagnosed with BC was 193 months (16.1 years) compared to 299 months (24.9 years) from transplantation for women not diagnosed with BC (p < 0.001). The transplanted women with BC have 4.3 times higher hazard of dying (p = 0.002) compared to those without. After adjusting for age, this difference decreases to 2.4 (p = 0.059). The median overall survival of the BC transplant patients was 35 months from cancer diagnosis. Regarding the incidence of BC in the total sample, there are approximately 13 new cases per 100,000 person-months. In the age groups ≤ 45, 46-60 and ≥61 years 2, 23 and 18 new BC cases per 100,000 person-months were recorded.

Conclusions

BC incidence appears increased in this population. BC diagnosis may adversely affect survival of renal transplant recipients. Further study of predisposing BC risk factors may reveal additional associations.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

231P - The changing landscape of breast cancer incidence after treatment for Hodgkin’s disease (ID 2017)

Presentation Number
231P
Lecture Time
12:00 - 12:00
Speakers
  • Amelia J. Benjamin (London, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer (BC) incidence increases after treatment for Hodgkin’s disease (HD). Over time, radiation techniques (RT) have reduced in dose and irradiated volume, and fewer alkylating (and gonadotoxic) chemotherapy (CT) agents used. We investigated BC incidence in the context of treatment changes over almost 4 decades and known risk factors.

Methods

PubMed abstracts were identified using search terms ‘Hodgkin disease’, ‘Breast neoplasm’ and ‘risk’. Articles in English between 01/01/1990-31/12/2018 reporting on risk of BC in HD survivors were included. Outcomes included relative risk (RR), standardized incidence ratio (SIR), absolute excess risk (AER), cumulative incidence (CI), hazard ratio (HR) and odds ratio (OR) of BC in HD survivors.

Results

30/245 articles were included. 6 report BC incidence alone (n = 7573). Other factors were RT dose and volume, CT, age at HD and its proximity to menarche and menopause. 10 studies looked at 2 factors (n = 34637), 7 at 3 factors (n = 15253), 4 at 4 factors (n = 5763), and 2 at 5 factors (n = 6110). 1 study was on radiation volume only (n = 734). SIR of BC ranged from 2.4-75.3; AER from 9.2-83.6/10,000 years; RR was 1.9-10.6. Variation is due to differences in cohort characteristics, and incomplete follow-up. BC incidence peaks 11-35 years post HD. Risk remains high at age 50-59 (SIR 3.8), when women are no longer annually screened. BC risk increases if RT is given within 6 months menarche (OR 5.52 (1.97–15.46). Earlier menopause reduces BC risk. BC risk increases linearly with increasing radiation dose. The OR can increase 11-fold with breast doses >40Gy compared to 0Gy. Mantle vs. mediastinal RT doubles HR. CT reduces the BC risk compared with RT alone. Newer RTs reduce BC risk; as a result, some studies demonstrate lower BC incidence in more recent treatment periods (SIR 3.2 in 1970s vs. 1.3 1990-2007). Other studies show no temporal change in incidence.

Conclusions

Reduction in BC risk from lower doses and volumes of RT may be offset by reduced CT gonadotoxicity from newer regimens and, therefore, the impact of treatment changes over 4 decades on BC incidence requires further investigation. Current guidelines on screening HD survivors need to be adapted to reflect the changes in treatment regimens.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

Is axillary lymph node dissection necessary in breast cancer patients with mastectomy and false-negative frozen section in sentinel lymph node biopsy? (ID 4853)

Lecture Time
12:00 - 12:00
Speakers
  • Jing Si (Jiaxing, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00
Poster Display session 2 Poster Display session

233P - Number of deliveries as a prognostic factor in different breast cancer subtypes (ID 1780)

Presentation Number
233P
Lecture Time
12:00 - 12:00
Speakers
  • Anniina Jääskeläinen (Oulu University Hospital, Finland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Some registry-based and population-based studies have suggested that high parity could be an adverse prognostic factor in luminal breast cancer, although the definition of breast cancer subtypes has been varied and prospective studies are lacking.

Methods

We report long-term follow-up (median 8.5 years) from prospectively collected single-institution material of early breast cancers. The patients (n = 612) were treated with modern treatment modalities in a Finnish university hospital clinic and clinicopathological surrogates of intrinsic subtypes were updated to match with the ESMO 2015 Early Breast Cancer Clinical Practice Guidelines. Long-term outcomes were recorded and special emphasis was given to exact reproductive factor anamnesis as a potential prognostic factor.

Results

Ten-year breast cancer-specific survival (BCSS) in this real-life prospective population was 91.4% in the whole cohort. The longest ten-year BCSS was observed in luminal A-like cancers (97.6%) and the worst in luminal B-like (HER2-positive) subgroup (80.6%). Having five or more deliveries associated with dismal BCSS (univariate p = 0.0015). When subtypes were assessed separately in multivariate analysis, this association remained significant only in luminal B-like (HER2-negative) cancers (HR 2.64; 95% CI 1.05-6.65; p = 0.04) when tumor size and nodal status were also included to the analysis. Having 5 or more deliveries also associated with node positivity in the whole cohort (p = 0.0016), but not with different subtypes.

Conclusions

This is the first prospectively collected study with the modern definition of breast cancer subtypes and contemporary treatments to assess parity as a breast cancer prognostic factor. Our results suggest that high parity is an adverse prognostic factor, but only in luminal B-like (HER2-negative) subtype. The biological effects of parity seem extend to later breast cancer and its metastasis in estrogen dependent, rapidly proliferating breast cancers.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

234P - Effects of supervised and adapted exercise program in the quality of life and strength of breast cancer survivors: MAMA MOVE Gaia trial (ID 4650)

Presentation Number
234P
Lecture Time
12:00 - 12:00
Speakers
  • Ana Joaquim (Vila Nova de Gaia, Porto, Portugal)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Treatments for early breast cancer have side effects that affect quality of life (QoL) and cause deconditioning. Physical exercise might have a supportive and coadjuvant role in the rehabilitation of breast cancer survivors. We aimed to analyse the preliminary results of a community-based supervised exercise training program on QoL and muscle strength in breast cancer survivors.

Methods

Twenty breast cancer female survivors were recruited to a single-arm clinical trial consisting of sequential 16 weeks (wk) of control phase (CP) and 16 wk intervention phase (IP). Four evaluations were carried out: M1 (8 wk on CP), M2 (immediately previous IP), M3 (8 wk CP) and M4 (16 wk IP). The IP consisted of 3 sessions per week of combined aerobic and strength exercise (60min) at moderate to vigorous exercise (65-85% of maximum heart rate or 6-8 points on OMNI scale). The primary endpoint was QoL, which was evaluated by EORTC QLQ-C30 questionnaire. Secondary endpoints included handgrip strength and sit-to-stand (STS) test.

Results

Of the 20 recruited women, 19 initiated and 15 concluded the program, with a mean compliance to the exercise intervention of 63.6%. The median age was 59 years old (39-72). All but 3 were diagnosed with invasive carcinoma. After surgery, 13 (62%) underwent radiotherapy, 15 (71%) chemotherapy and 18 (86%) were under hormonotherapy. During the control phase, no significant differences were observed in the efficacy variables. There was no changes over time for any domain of QoL, except for physical functioning scale (p = 0.038), where it was observed a trend to increase between M2 and M3 (77.3±14.0 to 85.3±10.1, p = 0.051). A significant increase in handgrip strength of non-operated (22.2±3.9 to 25.6±5.3 kg.f, p = 0.004) and operated limb (22.6±4.7 to 26.9±6.6 kg.f, p = 0.001) was shown after exercise training. Similar results were also observed for STS test [12 (11-13.5) to 17 (13-21) repetitions, p = 0.002].

Conclusions

An exercise program appears to be beneficial for QoL, particularly in the physical functioning of breast cancer survivors. Moreover, it seems to have an important role on strength levels.

Legal entity responsible for the study

Associação de Investigação e Cuidados de Suporte em Oncologia.

Funding

Liga Portuguesa Contra o Cancro.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

235P - Study on the socioeconomic and clinical factors affecting the proportion of breast conserving surgery in Chinese women breast cancer (ID 4962)

Presentation Number
235P
Lecture Time
12:00 - 12:00
Speakers
  • Jin Zhang (Tianjin, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

This study intends to investigate the socioeconomic and clinical factors affecting the proportion of breast conserving surgery (BCS) in China.

Methods

A total of 51237 breast cancer patients were treated in Tianjin Medical University cancer institute &Hospital from January 2005 to January 2018. In order to improve the success rate of BCS, we choose 5660 patients prepared to be treated by BCS to make analysis of independent factors affecting initial positive margins. Finally, we analyzed the survival trend of breast cancer patients after increasing the proportion of BCS by comparing the locoregional free survival (LRRFS), distant metastasis free survival (DMFS), overall survival (OS) of breast cancer patients.

Results

Multivariate analysis showed the distance from nipple (P = 0.030), tumor distribution along the duct (OR=2.599,P<0.001), pathological subtype (P < 0.001) and lymph node metastasis (OR = 0.299, P < 0.001), no preoperative MRI examination (OR = 1.291,p=0.001)were independent predictors of positive resection margins. Multivariate analysis revealed that tumor size(OR=0.706,P<0.001), non-mass enhancement (NME)(OR=4.443,P=0.001), malignant enhancement surrounding tumor (OR=1.647, P<0.001) were independent predictors of positive resection margins. The survival analysis of breast cancer patients after increasing the proportion of BCS revealed that the 5-LRRFS of 2005-2010 and 2011-2013 were 97.2%,98.4%, respectively. The 5-DMFS of 2005-2010 and 2011-2013 were 94.1%, 95.2 %, respectively, without significant difference. The OS of 2005-2010 and 2011-2013 were 96.4%, 97.9% respectively.

Conclusions

In China,we should gradually reduce the influence of socioeconomic factors on the proportion of breast conserving surgery in the future. Preoperative MRI should be encouraged in patients preparing for BCS. Clinicopathological characteristics and MRI findings are significantly associated with a positive resection margin in breast cancer patients.

Legal entity responsible for the study

The author.

Funding

The National Natural Science Foundation of China (81672623).

Disclosure

The author has declared no conflicts of interest.

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Poster Display session 2 Poster Display session

236P - Clinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program? (ID 5451)

Presentation Number
236P
Lecture Time
12:00 - 12:00
Speakers
  • Marco Giavarra (Udine, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance.

Methods

We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018.

Results

Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2-positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing.

Conclusions

The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

237P - The value of genetic counselling in breast cancer genetic testing and clinical management (ID 888)

Presentation Number
237P
Lecture Time
12:00 - 12:00
Speakers
  • Vicki Kiesel (Cambridge, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Multiple national1 and international2 guidelines recommend that genetic testing is provided by genetic experts in the context of genetic counselling. However, there has been little research performed assessing the utility of genetic counselling. This study was performed to determine the value of genetic counselling for individuals undergoing breast cancer genetic testing.

Methods

GeneHealth UK clinical records for patients seen between the 1st January 2018 and 30th June 2018 for breast cancer were reviewed to determine what was discussed during the consultations. Data was collated in four categories: a) appropriateness of genetic testing, b) psychological support, c) implications for relatives d) management guidance.

Results

Of a total of 130 patients, 74% (96) had breast cancer, and 26% (34) had a family history. 10% of tested patients had a pathogenic genetic variant. 98% of patients had at least one discussion in the assessed areas; 16% had two, 21% had three and 52% had four or more. Genetic counselling helped 15% of patients decide not to proceed with genetic testing: either because a relative would be more appropriate to test (5%), the patient had a low risk of a BRCA mutation (3%) or for psychological reasons (7%). Psychological support was provided to 15% of patients including the provision of support resources in 12% and referral for counselling in 2% of cases. Genetic counsellors assess the whole family and were therefore able to provide screening recommendations for relatives in 62% of cases and assess risk of other familial conditions in 2% of families. Of importance external referrals were made in 6% of patients.

Conclusions

Genetic counselling provides significant psychosocial and practical benefits in the provision of breast cancer genetics: including advice for the whole family, ensuring genetic testing is appropriate and referral to appropriate external healthcare agencies. 1 NICE Guidance 2 NCCN Guidelines.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Kiesel: Shareholder / Stockholder / Stock options: Genehealth UK. G. Wishart: Shareholder / Stockholder / Stock options: Check4Cancer.

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Poster Display session 2 Poster Display session

238P - Elderly patients in the Japanese breast cancer registry (ID 4005)

Presentation Number
238P
Lecture Time
12:00 - 12:00
Speakers
  • Masataka Sawaki (Nagoya, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Aim: To clarify the clinicopathological characters and treatments and prognosis in elderly breast cancer patients using the Japanese Breast Cancer Registry (JBCR) system.

Methods

We reviewed data from JBCR, which is the nation-wide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify its characteristics, we compared elderly patients aged 75 and over (elderly) with aged from 65 to 74 (young-old; y-o) and that from 55 to 64 (post-menopausal; p-m), respectively.

Results

In total 132,240 cases diagnosed between 2004 and 2011 were reviewed (elderly; n = 27,385, y-o; n = 43,839, p-m; n = 61,016). In histology, the proportion of mucinous carcinoma and apocrine carcinoma were higher in elderly (6.1%, 1.8%, y-o; 3.5%, 1.7%, p-m; 1.8%, 1.3%, respectively). Patients with clinical stage II and III were more frequent in elderly (45.1%, y-o; 39.0%, p-m; 39.8%). ER -positive rate was higher (76.8%, y-o; 76.3%, p-m; 72.7%) and HER2-positive rate was lower in elderly (10.5%, y-o; 12.8%, p-m; 18.6%, p < 0.001). As for surgery, the rate of breast conserving surgery (BCS) was lower in elderly (46.4%, y-o; 55.0%, p-m; 59.6%), and the rate of no surgery for axilla was higher in elderly (18.4%, y-o; 5.9%, p-m; 4.8%, p < 0.001). Irradiation after BCS was performed only in 41.3% of elderly patients, whereas y-o and p-m were 75.9%, 83.0%, respectively. Adjuvant chemotherapy was performed only in 10.8% of elderly patients, y-o and p-m were 31.8%, 46.2%, respectively. Half of elderly patients (49.8%) who underwent chemotherapy were given CMF or oral 5FU. As for hormone therapy, Tamoxifen was used more frequently in elderly (18.1%, y-o; 10.6%, p-m; 9.7%). The 5 years-survival analysis is shown in Table.

238P

Age≧7565-7455-64
Distant disease-free survival (%)93.194.393.1
Overall survival (%)84.393.794.4
Breast cancer-specific survival (BCSS) (%)94.296.795.9
Other disease death (%)48.035.820.6

Conclusions

Elderly patients suffered from more advanced disease at the time of diagnosis. Irradiation after BCS and primary systemic chemotherapy was more frequently omitted in the elderly patients. Overall, BCSS was similar among ages, but the rate of other causes of death was higher in elderly patients.

Legal entity responsible for the study

The authors.

Funding

Japanese Breast Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

239P - Tumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy (ID 3330)

Presentation Number
239P
Lecture Time
12:00 - 12:00
Speakers
  • Leonora De Boo (Amsterdam, Netherlands)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and their association with outcome and benefit of intensified platinum-based chemotherapy.

Methods

Patients in this study participated in a randomized controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993-1999 in stage III BC. Stromal TILs were scored according to International guidelines in these HER2-negative tumours. BRCA-profiles were determined using array-based Comparative Genomic Hybridization (aCGH) data.

Results

TIL levels were evaluated in 248 stage III breast tumours. High TILs are associated with TNBC. Tumours were classified as non-BRCA-like (n = 167), BRCA1-like (n = 30), BRCA2-like (n = 39) or BRCA1/2-like (n = 12). BRCA-like tumours harboured higher TILs compared to non-BRCA-like tumours (median TILs of 20% vs 10%, respectively, p < 0.01). TIL levels in BRCA1-like tumours were higher compared to BRCA2-like (median TILs of 20% vs 10%, respectively, p < 0.001) and non-BRCA-like tumours (median TILs of 10%, p < 0.001). These correlations remained significant within the ER-positive subgroup. Within TNBC, TIL levels were not higher in BRCA-like compared to non-BRCA-like tumours (median TILs of 30% vs 25%, respectively, p = 0.96). In this stage III BC cohort, high TIL level was associated with favourable outcome regarding recurrence-free and overall survival (TILs per 10% increment, HR 0.82, 95% CI 0.71-0.94, p = 0.01, respectively HR 0.80, 95% CI 0.68-0.94, p = 0.01). There was no significant interaction between TIL levels and benefit of intensified platinum-based chemotherapy.

Conclusions

In this high-risk breast cancer cohort, high TILs were associated with TNBC and BRCA1-like status. Within the ER-positive subgroup, TIL levels were higher in BRCA1-like compared to non-BRCA-like tumours, but this was not seen within the TNBC subgroup. When adjusted for clinical characteristics, TIL levels were significantly associated with a more favourable outcome in stage III BC patients.

Legal entity responsible for the study

The authors.

Funding

Dutch Cancer Society.

Disclosure

A. Cimino-Mathews: Research grant / Funding (self): BMS. S.C. Linn: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Cergentis; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Adienne; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentch; Research grant / Funding (institution): Tesaro. M. Kok: Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

240P - Unravelling the biological characteristics of MammaPrint extreme risk subgroups (ID 3971)

Presentation Number
240P
Lecture Time
12:00 - 12:00
Speakers
  • Rajith Bhaskaran (Amsterdam, Netherlands)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

MammaPrint® (MP) is a 70-gene based prognostic assay that stratifies early-stage breast cancer patients into low and high-risk of relapse. Recently, further stratification of the 70-gene risk results identified extreme low and high-risk subgroups with specific clinical outcomes (Delahaye et al. 2017) and treatment response characteristics (Wolf et al. 2017). However, the biological profiles of these extreme MP subgroups are not fully investigated. In this study, we aim to gain more insight into their biological significance using differentially expression genes (DEGs) analysis.

Methods

We selected 400 samples from the whole MP range and defined 4 subgroups (Ultra high [UH], High risk [HR], Low risk [LR], Ultra low [UL]), for which FFPE microarray full-transcriptome data were available at Agendia. DEGs analysis was performed with limma and subsequent pathway analysis with Enrichr and GOrilla.

Results

Two separate comparative analyses were carried out to unravel biological processes associated with extreme risk subgroups: UL vs. LR and UH vs. HR. We found 101 DEGs (logFC > =0.485 & FDR <0.05) between UL and LR subgroups and 1714 DEGs between UH and HR subgroups. Based on the pathway analysis, our results showed that the UL subgroup was more homogeneous, with enrichment in pathways reflecting low proliferative and metastatic features. This is in line with the favorable long-term outcome characteristic of the UL group. Conversely UH exhibited higher heterogeneity, with the enrichment of more diverse pathways including immune response, cell cycle and proliferation, that could be associated with genomic instability. This would support the recent finding of UH samples being more sensitive to veliparib/carboplatin combination therapy compared to HR samples (Wolf et al. 2017)). Furthermore, clustering approach demonstrated UH and other subgroups as two distinct clusters.

Conclusions

Our preliminary findings give additional insights into the biological processes associated with extreme MP groups, which might open new avenues for therapeutic intervention in breast cancer.

Legal entity responsible for the study

Agendia Inc.

Funding

Agendia Inc.

Disclosure

R. Bhaskaran: Full / Part-time employment: Agendia Inc. C. Griffioen: Full / Part-time employment: Agendia Inc. D. Wehkamp: Full / Part-time employment: Agendia Inc. L. Mittempergher: Full / Part-time employment: Agendia Inc. A.M. Glas: Full / Part-time employment: Agendia Inc.

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Poster Display session 2 Poster Display session

241P - Residual cancer burden as a prognostic factor in a large series of neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes (ID 5871)

Presentation Number
241P
Lecture Time
12:00 - 12:00
Speakers
  • Catalina Falo (Hospitalet de Llobregat, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Neoadjuvant chemotherapy offers the possibility to test chemo sensitivity in vivo. pCR is a good surrogate of survival. Other measures of pathological response include de residual cancer burden (RCB). The aim of our study is to assess prognostic factors of survival including RCB.

Methods

488 breast cancer (BC) patients treated with NATC based on anthracyclines and taxanes with trastuzumab in HER-2 positive between 2009 and 2016 at a single Institution. Chi-square test was run for the univariate analyses and a cox-regression was performed regarding prognostic factors. Survival was calculated with Kaplan-Meier survival plots since the start of NATC to the first documented disease recurrence (DDFS) or overall survival (OS) by using IBM SPSS version 23.

Results

Mean age was 51.13 (24-84). After a follow up of 63 (4-129) months there have been 14 (2.9%) local recurrences; 55 (11.3%) distant recurrences and 56 deaths (11.4%), 50 due to BC progression (10.2%). In the univariate analyses those factors related to distant recurrence were histology ductal vs lobular: 14.2 vs 35.7%, p: 0.032; molecular subtype: luminal A (15.2%) vs luminal B (14.2%) vs luminal B Her2 (11.8%) vs HER2 enriched (7.7%) vs triple negative (TN) (22.8%), p: 0.042; TstageT0 (0%), T1(12.5%), T2(12.3%), T3 (18.8%) and T4 (23.9%), p: 0.006; N stage N0 (9.6); N1 (12.8), N2 (17.5) and N3(27.3%), p = 0.063;pTstage pT0 (8.5%), pTis (9.7) pT1a+b(7.5%)pT1c(20.3 %), pT2(21.8%), pT3 (29.2%) and pT4 (100%), p = 0.000; pN stage pN0 (8.2); pN1mic (0%), pN1 (16.8), pN2 (32.2) and pN3(42.3%), p = 0.000 and the RCB 0 (3.2%) vs I (7.1%) vs II (16.5%) vs III (23.4%), p: 0.0001. The estimated 5y DDFS was for RCB0: 100%; RCBI: 98%; RCBII: 85% and RCBIII: 68%. The HR for RCB was 1.4 (95%IC, 1.2-1.6), per subgroups the log rank was for luminal A: 3.4, p: 0.330; for luminal B: 10.6, p: 0.03; for luminal B Her2: 7.9, p: 0.04; for Her2 enriched: 25, p: 0.000 and for TN 16, p: 0.003.

Conclusions

In our large series the RCB is reproducible as a surrogate of survival special in those chemo sensitive tumors such as Her2 and triple negative ones.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

242P - Clinical validation of CanAssist breast in a Spanish cohort (ID 5014)

Presentation Number
242P
Lecture Time
12:00 - 12:00
Speakers
  • Manjiri Bakre (Bangalore, Karnatala, India)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

CanAssist-Breast (CAB) is a prognostic test for predicting risk of distant recurrence within five years in hormone receptor positive early stage breast cancer patients. It is unique in that the test uses immunohistochemistry coupled with a support vector machine learning based algorithm to predict risk score and category (High or Low). It has been developed and validated on a mix of Asian and Caucasian patients. The test has been clinically validated in over 1000 retrospective patient samples. In this study, we present for the first time data on the performance of CAB in a single center study from Spain (Vall D’Hebron Institute of Oncology, Barcelona).

Methods

Post-surgical FFPE tumor blocks along with patient demographics and clinical follow up data up to a mínimum of five years were obtained from the hospital. CAB was performed on the tumor samples at the CAP and ISO 15189 accredited OncoStem reference laboratory in India. Distant Metastasis Free Survival (DMFS) and Hazard Ratio were used were computed using survival analysis. MedCalc software (Version 18.10.2) was used for all statistical analysis. The negative predictive value (NPV) was computed for establish the accuracy of prediction in the low risk group.

Results

Sixty-two percent of this cohort had stage II disease. Sixty-nine percent and 61% had node negative and Grade 2 disease respectively. The median at onset was 61 years. The DMFS in the low risk category was 98% and 85% for the high risk (P = 0.0032). The Hazard Ratio was 7.04 (95% CI: 1.93-25.73). The NPV was calculated to be 98%. To exclude any confounding effect of chemotherapy, survival analysis was done in the chemotherapy naïve sub-group. In the chemotherapy naïve sub-group, the DMFS for the low risk group was 100% and 85% for the high risk (P = 0.02). These are results of the interim analysis of the study at half way mark and complete study data will be presented at the time ESMO meeting.

Conclusions

CAB performs well in stratifying risk of recurrence in this Spanish cohort with the data matching performance shown earlier with the mix of Asian and Caucasian patients. In the absence of any inter-mediate risk category in CAB, it offers a cost effective alternative to existing prognostic tests providing definitive results to plan treatment of early stage breast cancer patients.

Legal entity responsible for the study

Manjiri M. Bakre.

Funding

Has not received any funding.

Disclosure

M. Bakre: Leadership role, Full / Part-time employment, Officer / Board of Directors, CEO and Founder: OncoStem Diagnostics Pvt Limted.

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Poster Display session 2 Poster Display session

243P - Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer (ID 2787)

Presentation Number
243P
Lecture Time
12:00 - 12:00
Speakers
  • Peter A. Fasching (Erlangen, Germany)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Neoadjuvant studies in breast cancer (BC) patients have well-demonstrated that attaining pathological complete response (pCR) is associated with improved event-free survival (EFS) and overall survival (OS); and the association is strong in triple negative BC (TNBC) subtype. This study aimed to comprehensively evaluate the association of pCR and survival outcomes in TNBC by incorporating most recent studies; and to explore the impact of different study settings, thresholds of hormone receptor positivity defining TNBC and adjuvant chemotherapy usage on this association.

Methods

A literature search of neoadjuvant studies in TNBC was conducted up to October 2018. Clinical trials (CTs), real-world evidence (RWE) studies and meta-analyses (MA) with EFS/OS reported by pCR outcome were included. Main analyses were restricted to pCR definition of absence of tumor in the breast and axillary nodes, which is aligned with FDA guidance. Hazard ratios (HRs) evaluating the association between pCR and EFS/OS were derived from meta-analyses using fixed-effect and random-effects models. To further quantify the association, meta-analyses were conducted to synthesize the published survival curves by pCR outcome. A random-effects frailty model was utilized to account for between-study variation.

Results

Four randomized CTs, 2 single-arm CTs, 18 RWE studies and 1 MA for a total of 4,330 patients with TNBC were included in this study. Achieving pCR was strongly associated with improved survival outcomes (HR of EFS: 0.26, 95% CI: 0.22-0.30; and HR of OS: 0.20, 95% CI: 0.16-0.25). HR results were similar across study settings of CTs, RWE and MA. TNBC definition and adjuvant chemotherapy use did not have significant impact on HR results. The meta-analyses showed numerically longer survival in studies that reported adjuvant chemotherapy usage compared with those which did not, irrespective of attainment of pCR.

Conclusions

This study confirms the strong association between pCR and survival outcomes in TNBC based on evidence synthesis from both clinical and real-world settings. In addition, this study suggests potential survival benefit of subsequent adjuvant therapy for TNBC patients who received neoadjuvant therapy.

Legal entity responsible for the study

Merck & Co., Inc.

Funding

Merck & Co., Inc.

Disclosure

P.A. Fasching: Advisory / Consultancy: Merck & Co., Inc. M. Huang: Full / Part-time employment: Merck & Co., Inc. J. Cortés: Advisory / Consultancy: Merck & Co., Inc. J. Zhao: Full / Part-time employment: Merck & Co., Inc. J. O’Shaughnessy: Advisory / Consultancy: Merck & Co., Inc. P. Hu: Full / Part-time employment: Merck & Co., Inc. A. Haiderali: Full / Part-time employment: Merck & CO., Inc. V. Karantza: Full / Part-time employment: Merck & Co., Inc. G. Aktan: Full / Part-time employment: Merck & Co., Inc. A. Briggs: Advisory / Consultancy: Merck & Co., Inc. S. Ramsey: Advisory / Consultancy: Merck & Co., Inc. C.Z. Qi: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. J. Xie: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. C. Gu: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. K. Qian: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. M. Yuan: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc. E.Q. Wu: Advisory / Consultancy, Employee of Analysis Group, Inc., which has received consulting fees from Merck & Co., Inc.: Merck & Co., Inc.

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Poster Display session 2 Poster Display session

244P - Immune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial (ID 4301)

Presentation Number
244P
Lecture Time
12:00 - 12:00
Speakers
  • Gaia Griguolo (Padova, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

In HR+/HER2- early BC, high tumour infiltrating lymphocytes (TIL) levels predict higher pathological complete response to neoadjuvant chemotherapy, but are associated with shorter overall survival (Denkert, Lancet Oncol 2018). HR+/HER2- BC is a biologically heterogeneous disease, encompassing all BC molecular intrinsic subtypes, with different clinical behaviour (Cejalvo, CTR 2018). Little is known concerning the distribution of TIL levels and immune infiltrate composition across intrinsic subtypes in HR+/HER2- BC.

Methods

Gene-expression data (Affymetrix platform) from pre-treatment frozen core-biopsies was available from 66 postmenopausal patients with HR+/HER2- early BC from the LETLOB trial (neoadjuvant letrozole+/-lapatinib) (Guarneri, JCO 2014). Intrinsic subtype was assigned using a research-based PAM50 subtype predictor. Relative leukocyte fractions were calculated using CIBERSORT (Newman, Nature Methods 2015), a deconvolution method based on RNA gene-expression signatures. Pre-treatment stromal TILs were assessed on centralized HES slides according to recommendations (Salgado, Ann Oncol 2015).

Results

Intrinsic subtype distribution was as follows: basal 18% (N = 12), HER2-enriched 8% (N = 5), Luminal A 39% (N = 25), Luminal B 36% (N = 24). Non-luminal subtypes (HER2-enriched and Basal) had significantly higher baseline TIL levels than luminal subtypes (median (range): 7 (0-100) and 2 (0-35), respectively; p = 0.038). Non-luminal subtypes also presented higher fractions of CD4 memory activated T-cells (p = 0.018), γδ T-cells (p = 0.010) and M1 macrophages (p = 0.001) and lower fractions of T-regulatory cells (p = 0.002) than luminal subtypes.

Conclusions

In HR+/HER2- early BC, non-luminal subtypes show higher TIL levels and a more pro-inflammatory anti-tumour immune infiltrate composition. This immune heterogeneity across intrinsic subtypes should be considered when analysing the complex prognostic role of TILs in HR+/HER2- early BC.

Clinical trial identification

NCT00422903.

Legal entity responsible for the study

University of Padua.

Funding

GlaxoSmithKline funded the clinical trial (LETLOB) including gene-expression analysis; DOR grants 1721185/17 and 1830512/18 from the University of Padua.

Disclosure

M.V. Dieci: Advisory / Consultancy: EliLilly; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: Celgene. A. Frassoldati: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Eisai. A. Prat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Amgen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Puma; Advisory / Consultancy: Oncolytics Biotech; Honoraria (institution), Research grant / Funding (institution): Nanostring; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Lilly. P.F. Conte: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: EliLilly; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck-KGa. V. Guarneri: Advisory / Consultancy, Speaker Bureau / Expert testimony: EliLilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

245P - Frequency of germline mutations in women’s cancer susceptibility genes in a large cohort of Chinese breast cancer patients (ID 3205)

Presentation Number
245P
Lecture Time
12:00 - 12:00
Speakers
  • Ning Liao (Guangzhou, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The prevalence of cancer related germline mutations in unselected Chinese breast cancer (BC) patients is unknown. Our study aims to examine the germline mutations prevalence and to investigate the relationship among tumor characteristics, somatic mutations and germline mutations.

Methods

Matched white blood cells and tumor tissue samples of 524 unselected Chinese BC patients (stage Tis to IV) were profiled using a panel consisting of 520 cancer-related genes. Germline mutations of 62 cancer susceptibility genes included all breast/ovarian cancer-related genes in the US genetic guidelines were assessed.

Results

A total of 76 pathogenic or likely pathogenic (P/LP) germline variants spanning 15 genes were detected from 58 patients (11%), with 29 and 38 mutations detected in BRCA1/2 and other cancer susceptibility genes, respectively. Overall, mutations detected included 11 BRCA1, 18 BRCA2, 4 MUTYH, 4 PALB2, 3 ATM, 3 BRIP1, 3 CDH1, 3 RAD51C, 2 CHEK2, 2 FANCA, 2 PMS2, 2 TP53, 1 FANCI, 1 FANCL and 1 PTEN. We detected 1968 germline mutations classified as variants of uncertain significance spanning all 62 cancer susceptibility genes from 490 patients (93%). We revealed young age, premenopausal status, and family history of breast/ovarian cancer were associated with P/LP germline mutations. Interestingly, somatic TP53 mutations were detected in all patients with P/LP germline BRCA1 mutations (100%, 11/11) and a majority (67%, 2/3) of patients with likely pathogenic CDH1 mutations. No somatic TP53 mutation was detected in patients with germline ATM and TP53 mutations. Somatic PIK3CA mutations were more frequently seen in patients with germline CDH1 (3/3). A patient with pathogenic germline PALB2 mutation (p.Q921fs) also has somatic PALB2 mutation (p.D525fs).

Conclusions

Our study derived the prevalence of P/LP germline mutation in 524 Chinese BC patients and 11% were found to have a germline mutation. We explored the characteristics of tumor somatic mutations in germline mutations carriers, which provided a better understanding of patients with germline mutations.

Legal entity responsible for the study

Ning Liao.

Funding

National Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768).

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

246P - Triple blinded prospective study assessing the impact of genomics & artificial intelligence Watson for oncology (WFO) on MDT’s decision of adjuvant systemic therapy for hormone receptor positive early breast carcinoma (ID 4091)

Presentation Number
246P
Lecture Time
12:00 - 12:00
Speakers
  • Somashekhar Sampige Prasannakumar (Bangalore, Karnataka, India)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Decision on adjuvant systemic therapy in hormone positive early breast carcinoma is the only grey area in breast carcinoma management. This study was done to investigate the concordance between the results of genomic test(Endopredict), artificial intelligence(Watson For Oncology,WFO) and tumor board decision and implications of the same in clinical practice.

Methods

This was a triple blinded, prospective study. Decision regarding the adjuvant systemic therapy was done by the multidisciplinary tumor board (MDT)after reviewing the pathology reports & the results correlated with Endopredict test reports & artificial intelligence(Watson for Oncology).

Results

Total of 42 patients included. Mean age was 58.3 years, 71.4% were post-menopausal. Breast conservation was done in 47.6%. 64.2% were T1-2N0 stage. Infiltrating ductal carcinoma was major type (83.3%). Decision by MDT to give adjuvant chemotherapy was for 25 patients (59.5%) & hormonal therapy for rest. Recommendation by Watson for oncology was to give adjuvant chemotherapy in 50%. Endopredict score (EPclin) resulted in a low-risk group of 22 patients (52.3%), while 15(47.6%) had a high risk EPclin score. Discordance between the endopredict test, Watson & tumor board was for 11 patients (26.1%): 3 patients had high risk score, but the tumor board decision was to give hormonal therapy due to the age factor. 8 patients had low risk score, but tumor board decision was to give adjuvant chemotherapy. Extremes of age, premenopausal status, intermediate grade & high Ki 67% values were the factors associated with discordance. The treatment decision changed for 4 patients (4/11, 36%) after reviewing the endopredict test and Watson recommendation.

Conclusions

Tumor board decision can be more scientific & evidence based with the help of genomics & a learnt colleague in the form of Watson for Oncology. Even though the clinical experience is the important determinant of adjuvant therapy, genomic test with artificial intelligence, which includes the scientific evidence, will guide in decision making. Long term follow up is needed for the validation in our clinical setting.

Legal entity responsible for the study

Manipal Hospital Ethical Committee.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

247P - Prognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis (ID 4359)

Presentation Number
247P
Lecture Time
12:00 - 12:00
Speakers
  • Anna Diana (Napoli, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC.

Methods

A population cohort of 441 primary invasive ER+/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Specific Survival (BCSS) according to 4 subtypes established on the basis of Ki67 value and PR expression rate (Subtype 1: PR ≥ 20%/Ki67<20%; Subtype 2: PR ≥ 20%/Ki67≥20%; Subtype 3: PR < 20%/Ki67≥20%; Subtype 4: PR < 20%/Ki67<20%). Cox regression analysis was used to correlate tumor characteristics with DFS and BCSS.

Results

The rates of progression disease were 8%, 19%, 30% and 12% in subtype 1, 2, 3 and 4, respectively. Low PR expression (<20%) resulted an independent poor prognostic factor for DFS in patients with high Ki67 value (≥20%). The median DFS was 12.6 months and 10.1 months in subtype 2 and subtype 3, respectively (p = 0.025) (Fig.1). The rates of cancer death were 5%, 12%, 24% and 12 % in subtype 1, 2, 3 and 4, respectively. Consistent with DFS results, a statistically significant correlation of PR expression level and BCSS was reported in patients with high Ki67 index (the median BCSS was 12.9 months in subtype 2 versus 10.5 months in subtype 3, respectively) (p = 0.04). No correlations between survival and PR expression were demonstrated in patients with low Ki67 value (<20%), probably due to the small sample size in the subtypes 1 and 4 groups.

Conclusions

Our study revealed different outcomes among patients with early BC according to different PR expression levels. Noteworthy, in patients with Ki67 ≥20%, low PR expression levels (<20%) could be considered as a prognostic marker suggesting to re-evaluate PR status as a potential therapeutic guide in ER+/Her2- early BC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Diana: Travel / Accommodation / Expenses: Ipsen, Novartis, Pharmamar, Italfarmaco. F. Carlino: Travel / Accommodation / Expenses: Italfarmaco, Gentili. E. Franzese: Travel / Accommodation / Expenses: Roche. S. Centonze: Travel / Accommodation / Expenses: Thesaro, Roche, Gentili. F. De Vita: Advisory / Consultancy: Roche, Amgen, Celgene, Lilly. F. Ciardiello: Advisory / Consultancy: Merck, Roche, Lilly, Bayer, Amgen, Pfizer, Servier. M. Orditura: Honoraria (self): Epionpharma, Italfarmaco; Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): EISAI. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

248P - PAM50 HER2-enriched subtype and pathological complete response in HER2-positive early breast cancer: A meta-analysis (ID 1369)

Presentation Number
248P
Lecture Time
12:00 - 12:00
Speakers
  • Francesco Schettini (Napoli, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

HER2-positive (HER2+) breast cancer (BC) comprises all the intrinsic molecular subtypes, with the HER2-enriched (HER2-E) usually being the most represented. Data coming from neoadjuvant trials of HER2+ BC treated with anti-HER2 containing regimens, with or without chemotherapy (CT), have shown that HER2-E tumors are more likely to achieve pathologic complete response (pCR) than non-HER2-E tumors. We decided to perform a meta-analysis combining all the available data in attempt to validate the ability of the HER2-E signature to predict pCR.

Methods

A systematic literature search was performed to identify clinical studies exploring the correlation between BC subtypes and pCR after neoadjuvant therapy (NAT) with anti-HER2 containing regimens in patients affected by HER2+ early BC. Primary analysis compared the association of gene signatures with pCR. Secondary analyses compared the association of gene signatures with pCR within hormone receptor (HR) positive (+) or negative (-) BC. Odds Ratio (OR) and 95% confidence intervals (CI) for pCR were extracted from each trial. A random-effect model was applied. The Higgins’ I2 was used to quantify heterogeneity.

Results

Sixteen studies (2,857 patients) were included; 4 investigated CT-free regimens. Various methods for assessing BC intrinsic subtypes were used across all trials. HER2-E subtype was significantly associated with pCR in all patients (OR: 3.32, 95% CI: 2.70-4.07, p < 0.001, I2=25%) and in HR + (OR: 3.40, 2.51-4.61, p < 0.001, I2=0%) and HR- (OR: 1.97, 1.10-3.54, p = 0.02, I2=46%) disease. In CT-free studies, HER2-E subtype was significantly associated with pCR in all patients (OR: 4.43, 2.34-8.38, p < 0.001, I2=0%) and in HR+ disease (OR: 4.79, 2.23-10.29, p < 0.001, I2=0%), but not within HR- tumors (OR: 2.18, 0.66-7.26, p = 0.20).

Conclusions

HER2-E subtype identifies patients with a higher likelihood of achieving a pCR following anti-HER2-based NAT, with or without CT. In the latter case, albeit limited by small casuistry, the association seems stronger in HR+ tumors. This suggests that strategies to escalate or de-escalate systemic therapy in HER2+ tumors would benefit from incorporating intrinsic subtypes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Schettini: Travel / Accommodation / Expenses: Pfizer and Celgene. T. Pascual: Advisory / Consultancy: Roche. P.F. Conte: Honoraria (self): BMS, Roche, EliLilly, Novartis, AstraZeneca; Advisory / Consultancy: Novartis, EliLilly, AstraZeneca, Tesaro; Research grant / Funding (self): Novartis, Roche, BMS, Merck-KGa; Research grant / Funding (self): Italian Ministry of Health, Veneto Secretary of Health, University of Padua. S. De Placido: Honoraria (self): Roche, Pfizer, AstraZeneca, Novartis, Celgene, Lilly and Eisai. L. Carey: Research grant / Funding (institution): Genentech / Roche, Novartis, Seattle Genetics, G1 Therapeutics, Immunomedics, Innocrin. C.M. Perou: Shareholder / Stockholder / Stock options: BioClassifier LLC; Advisory / Consultancy: BioClassifier LLC; Licensing / Royalties: Breast PAM50. A. Prat: Full / Part-time employment, An immediate family member employed: Novartis; Honoraria (self): Pfizer, Novartis, Roche, MSD Oncology, Lilly and Daiichi Sankyo; Advisory / Consultancy: NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb; Research grant / Funding (self): Roche, Novartis; Travel / Accommodation / Expenses: Daiichi Sankyo. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

249P - Assessment of CPS+EG, neo-bioscore and modified neo-bioscore in breast cancer patients treated with preoperative systemic therapy: A multicenter cohort study (ID 1058)

Presentation Number
249P
Lecture Time
12:00 - 12:00
Speakers
  • LING XU (Beijing, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

An accurate prognostic assessment of breast cancer patients after preoperative systemic therapy (PST) is critical for physicians to adjust the systemic treatments. While both CPS+EG and Neo-Bioscore provide a satisfactory prediction, they, however, have limitations due to the lack of targeted therapies in current clinical practice.

Methods

A retrospective multicenter cohort study was conducted from 12 participating hosipitals’ databases from 2006 to 2015. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were calculated using the Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. The detailed staging systems are summarized in Table. Wald test and maximum likelihood estimates in Cox proportional hazards model was used for multivariate analysis.

Results

A total of 1077 patients were enrolled. The CPS+EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS and OS (all P < 0.001). While in the same stratum of Neo-Bioscore score 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values <0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03).

249P Point assignment for the CPS+EG, neo-bioscore, and modified neo-bioscore staging systems

Cancer StageCPS+ EG ScoreNeo-Bioscore (7 points)Modified Neo-Bioscore (8 points)
Pretreatment Clinical Stage (CS)
I000
IIA000
IIB111
IIIA111
IIIB222
IIIC222
Post-treatment Pathologic Stage (PS)
0000
I000
IIA111
IIB111
IIIA111
IIIB111
IIIC222
Tumor Marker
ER negative111
Grade 3111
HER2-negative11
HER2-positive & no Trastuzumab2

Abbreviations: CPS+EG, clinical-pathologic staging system incorporating estrogen receptor–negative disease and nuclear grade 3 tumor pathology; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2.

Conclusions

The modified Neo-Bioscore could circumvent the limitation of CPS+EG or Neo-Bioscore. The access of appropriate treatment should be incorporated into the existing staging systems for more refined prognosis prediction.

Clinical trial identification

The trial protocol number: NCT03437837 Release date: February 19, 2018.

Legal entity responsible for the study

Xuening Duan AND Yimin Cui.

Funding

National Key Research and Development Program of China.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

250P - The concordance of treatment decision guided by oncotype and the PREDICT tool in early stage breast cancer (ID 1156)

Presentation Number
250P
Lecture Time
12:00 - 12:00
Speakers
  • Hadar Goldvaser (Toronto, Canada)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Decision on adjuvant chemotherapy for early breast cancer can be guided by genomic assays. PREDICT is a validated free online tool that estimates the benefit from adjuvant chemotherapy using clinical and pathological data. The concordance of expected clinical decisions guided by Oncotype analysis and the PREDICT in unknown.

Methods

A retrospective single center cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative, node negative disease, whose tumors were sent for OncotypeDX analysis. Estimation of 10-year overall survival (OS) benefit from 2nd generation chemotherapy was calculated using the PREDICT 2.1v tool. Omission of chemotherapy was expected to be advised when Oncotype recurrence score (RS) was ≤25 or when the estimated 10-year OS benefit by the PREDICT was <2%. The tests were considered concordant for women with RS ≤ 25 and estimated PREDICT benefit<2% or for women with RS > 25 and estimated PREDICT benefit ≥2%. Concordance was presented using percentages and the K coefficient. The impact on concordance of pre-specified histological features was assessed, including tumor size, intensity of ER and progesterone receptor (PR), grade, Ki67 and perineural and lymphovascular invasion. The difference between the subgroups was calculated using Chi-squared test.

Results

A total of 445 women were included. Overall concordance was 75% (K = 0.284), with 55 (12.5%) women with low RS but estimated PREDICT benefit ≥2% and 55 (12.5%) with high RS and estimated PREDICT benefit<2%. The concordance was significantly higher for grade 1 disease compared to grade 2-3 (93% vs 72%, p < 0.001), tumor ≤1cm compared to > 1cm (85% vs 72%, p = 0.009), PR positive compared to PR negative (78% vs 58%, p < 0.001) and ki67<20% compared to ≥ 20% (82% vs 54%, p < 0.001). The intensity of ER and the presence of perineural or lymphovascular invasion had no significant impact on concordance.

Conclusions

Compared to PREDICT, using Oncotype in node negative, ER positive disease is expected to change clinical decision in a quarter of patients. The concordance is influenced by pathological features. The use of Oncotype may not be necessary for clinically very low risk patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Goldvaser: Honoraria (self): Roche. R. Yerushalmi: Honoraria (self): Roche; Honoraria (self): Medison; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Teva. M. Sarfaty: Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): Medison; Honoraria (self): Novartis. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

251P - Influence of first treatment delay on survival among breast cancer subtypes (ID 3447)

Presentation Number
251P
Lecture Time
12:00 - 12:00
Speakers
  • Irene Zarcos Pedrinaci (Marbella, Málaga, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Conflicting results on the the impact of cancer first treatment delay (FTD) on survival have been reported between several studies, and its importance has yet to be determined. We currently do not have any study in breast cancer (BC) analyzing how FTD influences the prognosis of the patients according to different inmunophenotypes. We conducted a study where we examined the relationship between survival and three periods of diagnostic-therapeutic delay, 30, 60 and 90 days.

Methods

This multicentre cohort study included BC patients from screening CAMISS PROJECT, during 2000-2006 with follow-up until 2014. Cox regression analysis, crude and multivariate, was applied to estimate risk of death. The Hazard Ratio (HR) was adjusted by FTD, stage, immunophenotypes of BC and comorbidity

Results

The study included 738 women aged 45-69 years. Median time of FTD was 58 days. First treatment aplied was surgery for all populations. 42% of BC presented as stage I and 34% stage II. 24% of patients had comorbidities. 21% expressed HER2, 80% estrogen receptors and 61% progresterone. There were 53% of Luminal A tumors, followed by 27% Luminal B, of which 10% also expressed HER2, 9% were HER2 overexpressing tumors, and 11% triple negative. In the crude analysis none of the three FDT cut-off points had a significant relationship with overall survival. Multivariate analysis adjusted for phenotypes, comorbidity and stage, showed worse prognosis tendency in DT30 and DT90, with a statistically significant level in DT60, hazard ratio [HR] 1,57; 95% IC (1,04-2,38). When we analyzed survival according to DT60 and BC subtypes there was more significant risk of death among HER2 subtype HR 2,91; 95% IC (1,63-5,21) and triple negative HR 1,90; 95% IC(1,01-3,60) comparing to Luminal A. No relationship was seen in Luminal B; Table.

251P

aHR30aHR60aHR90
Treatment delay (days)<30Ref
 > =301,53 (0,84-2,78)
<60R
 > =601,57 (1,04-2,38)
<90Ref
 > =901,72(1,00-2,95)
StageIRefRefRef
InSitu0,29 (0,07-1,24)0,29 (0,07-1,23)1,47 (0,89-2,44)
II1,40 (0,84-2,33)1,38 (0,83-2,30)3,01 (1,67-5,41)
III4,42 (2,66-7,35)4,43 (2,67-7,35)1,95 (1,02-3,72)
FenotipeLuminal ARefRefRef
Luminal B1,40 (0,85-2,31)1,45 (0,88-2,40)0,29 (0,07-1,22)
Her22,89 (1,62-5,18)2,91 (1,63-5,21)1,38 (0,83-2,31)
Triple Negative1,96 (1,01-3,66)1,90 (1,01-3,60)4,23 (2,56-7,01)
ComorbidityAbsenceRefRefRef
Presence1,63 (1,06-2,52)1,61 (1,04-2,48)1,59 (1,03-2,46)

Conclusions

Waiting 60 days to initiate treatment was associated with a significantly worse overall survivall among triple negative and HER2 BC. We consider it of importance to offer early treatment to aggressive BC subtypes.

Legal entity responsible for the study

REDISSEC-CAMISS Group-(Research Network in Health Services in Chronic Diseases).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

252P - Clinical features of early-stage (I-III) triple-negative breast cancer (TNBC) patients with tumours exhibiting low-overall change in molecular profile after neoadjuvant therapy (ID 3505)

Presentation Number
252P
Lecture Time
12:00 - 12:00
Speakers
  • Nour Abuhadra (Houston, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Seth et al. (ASCO 19) identified four biologic classes based on longitudinal molecular profiling of TNBC tumors pre- and post- neoadjuvant adriamycin/cyclophosphamide (AC). The four groups were defined based on the enriched and depleted hallmark pathways that were observed. The low-overall change (LOC) group was defined as having no significant change in the pathways in pre- and post-AC biopsies. Of note, this group of patients had lower pathological complete response (pCR) rates. The aim of this study is to describe the clinical features of early-stage (I-III) TNBC patients with tumors exhibiting LOC in their biopsies with neoadjuvant therapy.

Methods

We analyzed the clinical characteristics of 48 patients with early stage (I-III) TNBC enrolled in the ARTEMIS trial (NCT02276443). All patients received neoadjuvant AC; 48% of patients were subsequently treated on a clinical trial and 52% received standard taxane-based chemotherapy. We compared the clinical characteristics of 17 patients in the LOC group with 31 patients in the other three biologic classes. Two-group comparison was performed using Chi-squared test.

Results

Age at diagnosis, histology, Vanderbilt subtype, Ki-67, sTIL levels and vimentin expression were similar between the groups. Median age at diagnosis in the LOC group was 58 (range, 27-74). All patients in this group were stage II-III, with no stage I identified. 59% of patients in the LOC group had stage III disease compared with 26% in the other groups (p = 0.02), Also, 47% of patients in this group had AR ≥ 10% compared to 19% in the other biological groups (p = 0.04).

252P

VariableGroupLow-Overall Change Group (n = 17)%Other Biologic Classes (n = 31)%p
Age at diagnosis≤60105925810.10
>60741619
StageI00619N/A
II74117550.36
III10598260.02
HistologyInvasive ductal158826840.23
Metaplastic00413
Apocrine1600
Other1613
Vanderbilt subtypeBL3188260.24
LAR42426
M/MSL3181135
IM212412
Ki-67 (%)≥ 5084721680.16
< 509531032
Androgen Receptor Expression (%)≥ 108476190.04
< 109532581
Vimentin Expression (%)≥502124130.91
<5015882787
sTILLow (<5)74115480.37
Moderate (≥5-30)9521135
High (>30)0013

Conclusions

Patients with low-overall change in their tumors had later-stage disease and higher AR expression. Previous analysis by Seth et al. has demonstrated a lower pCR rate in this group with standard neoadjuvant chemotherapy. This analysis highlights the potential role of androgen deprivation in this class of tumors.

Legal entity responsible for the study

The authors.

Funding

The University of Texas MD Anderson Cancer Center Moonshots Program and a CPRIT Multi-Investigator Research Award (MIRA).

Disclosure

S. Moulder: Research grant / Funding (self): Pfizer; Research grant / Funding (self): Genentech; Research grant / Funding (self): Novartis; Research grant / Funding (self): Seattle Genetics; Research grant / Funding (self): EMD Serono; Research grant / Funding (self): Bayer; Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

253P - Meta-analysis in HER2+ early breast cancer therapies and cost-effectiveness in a Brazilian perspective (ID 5442)

Presentation Number
253P
Lecture Time
12:00 - 12:00
Speakers
  • Marcos Magalhaes (Santo Andre, Brazil)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

HER2-targeted therapy was a paradigm shift for breast cancer. However, the optimal duration of adjuvant trastuzumab remain unknown. This issue is important in lower and middle-income countries such as Brazil where financial resources are scarce. The aim of this study is to determine which patients will benefit most with the addition of Pertuzumab to trastuzumab [T+P], trastuzumab for 12 months [T12] or trastuzumab for 6 months [T6].

Methods

Individual data meta-analysis was performed using 5 studies (Persephone, Phare, Horg, Aphinity and Katherine) for the intention to treat (ITT) population. Through pooled analyzes of the Persephone, Phare and Horg studies, we compared 12 months and 6 months of trastuzumab. The comparison between T+P and T6 was performed through an indirect comparison using Bayesian methodology. For cost-effectiveness analysis, we compared the treatment lining up in pairs exclusively considering the data from the Aphinity (T+P vs T12), Persephone (T12 vs T6) and Katherine (T12 vs T-DM1), setting a 30 years period of time and costs of adjuvant treatments and after progression in the Brazilian perspective.

Results

Individual data were analyzed from 12,753 patients. Patients who progressed in a 4-year period were 7.1% for T + P, 10.2% for T12 (HR 1.37, 95% CI 1.16-1.63) and 12.9% for T6 (HR 1.73, 95% CI 1.45-2.06). Regarding DFS in the N+ subgroup, T+P showed HR 0.77 (95% CI 0.62-0.96) and 0.74 (95% CI 0.49-1.11) compared to T12 and T6, respectively. Among patients N-, T+P compared to T12 showed a HR 1.13 (95%CI 0.68-1.86) and compared to T6 HR 0.83 (95%CI 0.45-1.52). ER+ patients, T+P showed HR 0.86 (95%CI 0.66-1.13) compared to T12 and HR 0.74 (95%CI 0.49-1.11) to T6. Among ER-, the values were HR 0.76 (95%CI 0.56-1.04) and HR 0.59 (95%CI 0.41-0.85), respectively. In the cost-effectiveness analysis, T+P demonstrated an ICER of $ 332,903 compared to T12, while T12 set side by side of T6 resulted in $ 42,774. In the subgroup N+, T+P presented $ 308,019 when compared to T12. T-DM1 was considered a cost-effective treatment with $ 3,031 compared to T12.

Conclusions

The combination T+P presented an benefit in the subgroup N+, but it was not considered cost-effective. T6 may be considered a therapeutic option in low budget scenarios for patients HR+/N-.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

254P - Anti-mullerian hormone (AMH) levels and antral follicle counts (AFC) may predict ovarian reserves before systemic chemotherapy (SC) in women with breast cancer (BC): A prospective clinical study (ID 1570)

Presentation Number
254P
Lecture Time
12:00 - 12:00
Speakers
  • Cetin Ordu (Istanbul, Balıkesir Province, Turkey)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Systemic chemotherapy (SC) has a negative effect on ovarian functions. The aim of this study is to investigate the effect of SC on anti-müllerian hormone (AMH) levels, antral follicle counts (AFC) and ovarian volumes (MOV) in patients with BC.

Methods

The demographic, clinical and pathological features of premenopausal breast cancer (BC) patients who were operated in the Istanbul Florence Nightingale Hospital were recorded. AMH levels, AFC and MOV measurements were performed before and after adjuvant SC in 3-month periods. The patients who did not have menstruel cycles for 6 months or longer had been classified as chemotherapy induced amenorrhea (CIA). The effects of different chemotherapy regimens on AMH, AFC and MOV in terms menstruel cycles resumption and CIA were investigated.

Results

Seventy one patients were eligible for the study, and median age of them was 38 years (ranged from 23 to 51 years). Median follow-up was 37 months (ranged from 20 to 51 months), CIA developed in 62% of patients. AMH, AFC, and MOV significantly decreased one year after SC (p < 0.0001). AMH before chemotherapy (median: 1,520 vs 0,755, p = 0.001), at the end of first year (median: 0,073 vs 0,010 ng/ml, p = 0.030) and pre-treatment AFC (median12 vs 4,50, p = 0.026) was lower in patients with CIA comparing those without CIA. In multivariate logistic regression analysis, AMH levels (OR:0.273, 95%: 0.102 – 0.733, p = 0.010) and AFC (OR: 1,180, 95% CI; 1,016-1,369, p = 0.030) before SC were the most valuable and earliest factors to predict CIA. There were no significant relationships between age of the patients (≤30vs>30 ), BMI (30vs> 30), SC regimen and number of cycles (4 vs > 4) and CIA (p > 0.05).

254P muitivariet analyses with logistic regrettion for CIA

UNIVARIETMULTIVARIET
OR95% CIOR95% CI
ER0,190,038-0,8910,0350,0020,000- 0,1110,002
HER 20.800,435-2,9361,130
ALND PERFORMED1,750,653-4,7020,265
AMH-10,640,454-0,9140,0140,2730,102- 0,7330,010
AMH-50,230,063-0,8120,0230,0090,000- 0,7540,037
AFC-10,870,780-0,9610,0070,7350,572- 0,9440,016
AFC-50,930,741-1,1650,527
MOV-11,000,987-1,0210,686
MOV-50,980,854-1,1580,790
TAXANE/W&İTHOUTTAXANE0,710,267-1,9100,503
TC/AC0,850,209-3,4910,825
AGE 354,661,613-13,4980,004
CHEMONUMBER0,240,080-0,7660,017
BMI 252,570,929-7,1180,069

Conclusions

SC significantly decreases AMH and AFC values independently of chemotherapeutic agents in patients with BC. The low AMH levels and less AFC before SC may predict CIA.

Legal entity responsible for the study

İstanbul Demiroğlu Bilim University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

255P - Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy (ID 2698)

Presentation Number
255P
Lecture Time
12:00 - 12:00
Speakers
  • Giuseppe Cancello (Milan, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Triple negative breast cancers are a heterogeneous group of breast cancer candidate to adjuvant chemotherapy in a large majority of cases. However, literature data indicate that the diagnosis of special types of breast cancer might be associated with a different outcome if compared with invasive ductal carcinoma with similar biological features and stages. Selected triple negative apocrine breast cancer can have an extremely good prognosis.

Methods

Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated between January 1998 and December 2016 at European Institute Oncology, Milan, we identified 24 patients with pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤20% who did not receive adjuvant chemotherapy. We compared the outcome of this cohort with a similar group of 48 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features (matching ratio 1:2).

Results

The median age was 63 and 50 years in the apocrine and ductal group, respectively. The mean value of Ki-67 expression was 12% in the apocrine group and 14% in the ductal group. 83% of apocrine tumors had size less than 2 cm, compared with 71% of ductal tumors. After a median follow-up of 6.6 years no patients in the apocrine group experienced a breast cancer related event compared with 12 events (including 5 loco-regional recurrences, 3 distant recurrences e 4 contralateral tumors) in the ductal carcinoma group (Gray test p-value=0.015).

Conclusions

The outcome of selected apocrine triple negative breast cancer patients is excellent and possibly deserves a treatment de-escalation. Multicenter projects focusing on the possibility to avoid adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Cancello: Honoraria (self): Pierre Fabre. E. Montagna: Honoraria (self): Pierre fabre; Honoraria (self): gentili. E. Munzone: Honoraria (institution), Advisory / Consultancy: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Genomic Health. S. Dellapasqua: Travel / Accommodation / Expenses: Roche. M.A. Colleoni: Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: OBI Pharma; Advisory / Consultancy: Puma Biotechnology; Advisory / Consultancy: Celldex; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

256P - Novel blood based circulating tumour cell biomarker for breast cancer detection (ID 3104)

Presentation Number
256P
Lecture Time
12:00 - 12:00
Speakers
  • Chun-Yu Liu (Taipei, Taiwan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

There is an unmet need for a blood test to detect breast cancer in women with dense breast tissue or clinically aggressive subtypes that may be missed by mammograms. Cell-free DNA in blood has shown 15-58% sensitivity for breast cancer. We evaluated the performance of a circulating tumor cell (CTC) assay as a complimentary biomarker for detecting breast cancer in an Asian population, which has high incidence of dense breast tissue.

Methods

A single-center, IRB-approved, prospective and blinded clinical study was conducted on 114 Taiwanese females with biopsy-confirmed breast cancer, and 50 healthy controls confirmed by ultrasound or mammogram. Four milliliter of blood was collected prior to imaging and processed using the CellMax biomimetic platform (CMx) which enumerates CTCs utilizing selection criteria based on a set of markers (cytokeratin 18, mammaglobin, CD45), cell morphometry (size, N/C ratio) and nucleus morphology. Logistic regression models for CMx CTC counts and patient age were used to assess the classification performance of the CMx test.

Results

Of the 114 cancer (80% were stage 0∼2), the subtypes were confirmed for 102 (62% ER/PR+ HER2-, 22% HER2+, 16% TNBC). CTC count was a significant predictor of cancer status (Likelihood Ratio P-value = 0.0001). At 90% specificity (exact 95% CI: 78.2%, 95.6%) sensitivity was 56.3% (95% CI: 43.3%, 68.6%) for the most common subtype ER/PR+HER2-, 36.4% (17.2%-59.3%) for HER2+, 43.8% (19.8%- 70.1%) for TNBC, 46.5% (37.1%- 56.1%) overall. Sensitivity was 62.5% (35.4%- 84.8%) for late stage (Stage III/IV cancer) and 43.5% (33.2%- 54.2%) for early stage (Stage 0, I or II cancer) patients. In the subset of 41 individuals with an indeterminate classification of BIRADS 3 (likely benign) or BIRADS 4 (likely malignant) sensitivity was 90% and specificity was 47.6% (95% CI: 25.7%, 70.2%).

Conclusions

In this initial study, CTC was a significant predictor of cancer. The CTC assay can easily be combined with cfDNA to enhance detection rates. Proof-of-concept data suggests potential for a rule out test to avoid unnecessary follow-up/biopsies in BIRADS 3/4 patients.

Legal entity responsible for the study

CellMax Life.

Funding

CellMax Life.

Disclosure

F. Lin: Shareholder / Stockholder / Stock options: CellMax Life. J. Wu: Shareholder / Stockholder / Stock options: CellMax Life. H.B. Hsieh: Shareholder / Stockholder / Stock options: CellMax Life. S. Chang: Shareholder / Stockholder / Stock options: CellMax Life. M. Javey: Shareholder / Stockholder / Stock options: CellMax Life. D. Watson: Shareholder / Stockholder / Stock options: CellMax Life. R. Mei: Shareholder / Stockholder / Stock options: CellMax Life. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

257P - Multi-gene prognostic signatures and prediction of pathological complete response of ER-Positive HER2-negative breast cancer patients to neo-adjuvant chemotherapy (ID 4631)

Presentation Number
257P
Lecture Time
12:00 - 12:00
Speakers
  • Claudia Mazo (Dublin, Ireland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Determining which early stage breast cancer patients should receive chemotherapy is an important clinical and economic issue. Chemotherapy has many adverse side effects, impacting on quality of life, along with significant economic consequences. Biomarkers that can predict patient response to chemotherapy can help avoid ineffective overtreatment. The aim of this work is to assess if the OncoMasTR (OM) signature can predict pathological complete response (pCR) to neo-adjuvant chemotherapy, and to compare its predictive value with EndoPredict (EP) and Oncotype DX (RS).

Methods

Gene expression datasets derived from breast cancer patients that had pre-treatment biopsies, received neo-adjuvant chemotherapy and an assessment of pCR were obtained from GEO (GSE16716, GSE20271, GSE25066, GSE32646, GSE34138, GSE41998, GSE22226). Patients with ER-positive, HER2-negative disease and pCR data were selected. OM, EP and RS numeric risk scores were approximated by applying the gene coefficients to the corresponding mean probe expression values. Association with pCR was estimated using logistic regression.

Results

A total of 813 patients with 66 pCR events were included in the analysis. OM, EP and RS prognostic scores were moderately well correlated according to the Pearson’s correlation coefficient: OM vs EP (min=0.44; mean=0.67; max=0.81), OM vs RS (min=0.34; mean=0.62; max=0.79), and RS vs EP (min=0.55; mean=0.79; max=0.89). Significant predictors of pCR with p-values of 0.0001 for all three signatures. Odds ratios for a 1 standard deviation increase in risk score, adjusted for cohort, were similar in magnitude and not significantly different: OM 1.66 (1.29 to 2.16), EP 1.76 (1.37 to 2.27), RS 1.84 (1.44 to 2.35).

Conclusions

In this in silico analysis, OM, EP and RS prognostic scores were significantly predictive of pCR to neo-adjuvant chemotherapy in ER-positive, HER2-negative breast cancer. Optimal stratification for neo-adjuvant chemotherapy offers the opportunity for personalised care, improved therapy response rates, and reduced ineffective treatment and costs.

Legal entity responsible for the study

University College Dublin.

Funding

The EI and from the European Union’s Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713654.

Disclosure

The author has declared no conflicts of interest.

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Poster Display session 2 Poster Display session

258P - Impact of menopause status on breast cancer outcomes and amenorrhea incidence during adjuvant tailored dose dense chemotherapy (ID 4632)

Presentation Number
258P
Lecture Time
12:00 - 12:00
Speakers
  • Andri Papakonstantinou (Stockholm, Sweden)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Adjuvant dose-dense chemotherapy improves breast cancer (BC) outcomes compared to standard chemotherapy, with no increase in chemotherapy-induced amenorrhea (CIA). However, the impact of menopausal status and the contribution of CIA to outcomes per subtype remain unclear.

Methods

PANTHER is a phase 3 trial comparing tailored, according to hematologic nadirs, and dose-dense (tdd) epirubicin/cyclophosphamide (EC) and docetaxel (D) versus standard interval FEC/D. The primary endpoint of the trial is relapse-free survival (BCRFS). This exploratory secondary analysis aimed to evaluate whether there was differential efficacy of tdd therapy according to menopausal status and if differences in CIA, defined as amenorrhea at 2 years following treatment, may contribute to its efficacy.

Results

Baseline menopause status was available for 1913 women; 1036 premenopausal and 877 postmenopausal. Median follow-up was 5.3 years. The administration of tdd EC/D was associated with a non-statistically significant improvement in BCRFS in both premenopausal (HR = 0.83, 95% CI 0.59 – 1.16, p = 0.265) and postmenopausal patients (HR = 0.74, 95% CI 0.51 – 1.06, p = 0.102; pinteraction0.658). On the contrary, a significant interaction was noticed in women with triple negative BC (TNBC, p = 0.043). Tdd EC/D improved BCRFS in postmenopausal women (HR = 0.44, 95% CI 0.19 – 1.03, p = 0.06) but had a trend to opposite effect among premenopausal women (HR = 1.29, 95% CI 0.69 – 2.40, p = 0.426). There was no difference in CIA rates between the two treatment groups (OR = 1.04, 95% CI 0.77 – 1.39).

Conclusions

Tdd EC/D was associated with non-significant improvements in BCRFS, regardless of menopause status, without increasing rates of CIA. Negative effect on TNBC could be a chance finding due to low number of patients but the results warrant caution and necessitate further investigation.

Legal entity responsible for the study

The authors.

Funding

Swedish Cancer Society, Swedish Breast Cancer Association (BRO), Radiumhemmet Research funds, Amgen, Roche, Sanofi-Aventis.

Disclosure

G. Steger: Honoraria (self): Amgen. R. Greil: Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self): BMS; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Janssen; Research grant / Funding (self): Roche; Research grant / Funding (self): BMS; Research grant / Funding (self): AstraZeneca. S. Loibl: Research grant / Funding (institution): Vigor; Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Pfizer; Honoraria (institution): Roche; Honoraria (institution): Puma; Honoraria (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Puma; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Teva. M. Gnant: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self): Invectys; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Nano string; Honoraria (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): Medison; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Medison. V. Moebus: Honoraria (self): Amgen; Honoraria (self): Celgene; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Myelotherapeutics; Honoraria (self): AstraZeneca. T. Foukakis: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Novartis; Honoraria (self): UptoDate. J. Bergh: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi-Aventis; Honoraria (self): Uptodate. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

259P - Progesterone receptor isoform ratio dictates antiprogestins/progestins effects on metastatic breast cancer models (ID 4732)

Presentation Number
259P
Lecture Time
12:00 - 12:00
Speakers
  • Maria F. Abascal (Buenos Aires, Argentina)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The use of progesterone receptor (PR) ligands for adjuvant breast cancer treatment remains controversial. We propose that antiprogestins inhibit the breast tumor growth with high isoform A (PRA)/isoform B (PRB) ratio while progestins may inhibit those with opposite ratios.

Methods

We used metastatic models with different PR isoform ratios to evaluate the effect of antiprogestins [mifepristone (MFP), aglepristone (AGLE), telapristone acetate (TLP), ulipristal acetate (UPA), or progestins [medroxyprogesterone acetate (MPA) or progesterone (Pg)]. Murine BALB/c tumors with PRA>PRB (C7-2-HI) and PRB>PRA (C7-HI), human MDA-MB-231 cells transfected with PRB and the inducible MDA-MB-231-iPRAB cells were inoculated into NSG mice.

Results

All antiprogestins inhibited C7-2-HI tumor growth rate (MFP 88%, TLP 59% UPA 70%) and the onset of lymph node and lung metastasis. AGLE induced complete tumor regression. The progestin MPA, increased tumor size and metastasis in a 60% (p < 0.001) and Pg showed a similar trend (22%). MFP and AGLE also inhibited the tumor growth and number of metastatic foci of the MDA-MB-231-iPRAB expressing PRA. Onset of long-term metastasis was evaluated by tumor surgery after interruption of MFP or AGLE neoadyuvant treatment. Both antiprogestins increased the Disease Free Survival rate (p < 0.001) compared with controls. Six out of 8 and 3/5 mice receiving AGLE and MFP, respectively, are disease free one year after surgery. AGLE adjuvant treatment, also inhibited long-term metastasis (p < 0.001). With C7-HI model (PRB>PRA), AGLE, UPA or MFP increased tumor growth and/or metastasis (p < 0.001) whereas MPA showed an opposite trend in the number of metastatic foci. Experiments performed with the MDA-MB-231 cells transfected with or induced to express PRB confirmed the inhibitory effects of MPA on the metastatic development.

Conclusions

Progestins/antiprogestins stimulate or inhibit, respectively tumor growth/metastasis of mammary carcinomas with high PRA/PRB ratio, and they may exert opposite effects in tumors with low PRA/PRB ratio. These findings highlight the relevance of evaluating PR isofor.m ratio prior to PR ligand treatment on human breast cancer.

Legal entity responsible for the study

CONICET.

Funding

CONICET; INC, ANPCYT.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

260P - PAM50 and CGH-array genomic characterization of HER2-equivocal breast cancers defined by the 2018 ASCO/CAP recommendations (ID 5737)

Presentation Number
260P
Lecture Time
12:00 - 12:00
Speakers
  • Carine Ngo (Paris, France)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

HER2 breast cancer status determines patients’ eligibility for targeted therapy. HER2 level of amplification is associated with a better response to anti-HER2 therapy. Benefit of anti-HER2 therapy for equivocal cases remains debated.

Methods

We aimed to better characterize HER2-equivocal breast cancers by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) according to 2018 ASCO/CAP guidelines using PAM50 gene expression-based molecular subtyping and to investigate genome-wide copy number alterations of these cases. PAM50 (nCounter assay; Nanostring) was performed on RNA from FFPE samples of 60 HER2-equivocal cases. These cases were subsequently analyzed by Agilent 60-mer oligonucleotide microarrays for array-based comparative genomic hybridization (aCGH).

Results

The 60 HER2-equivocal cases were classified as Luminal B in 31 cases (52%), HER2-Enriched in 14 cases (23%), Luminal A in 13 cases (22%) and Basal-like in 2 cases (3%) using PAM50. By IHC, 52 cases (87%) were ER+, 43 (72%) were also PgR+, 40 (67%) were grade III and 45 (75%) showed a high Ki67 > 20%. With aCGH, 23 cases (38%) presented chr 17q large copy number gain, 14 (23%) showed segmental copy number gain including HER2, 10 (17%) showed HER2 amplification, one (2%) showed a large copy number loss and 12 cases (20%) didn’t show any copy number alteration of the chr 17. Out of the 14 PAM50 HER2-Enriched cases, only 5 showed HER2 genomic amplification (Table). In total, 14 cases (23%) were discordant between molecular classification and genomic alteration status of the chr 17.

260P

Genomic alterations of chromosome 17Basal- likeHER2- EnrichedLuminal ALuminal BTotal
HER2 amplified052310
Large copy number gain0151723
Segmental copy number gain254314
No alteration032712
Large copy number loss00011
Total214133160

Conclusions

Using PAM50, the majority of HER2-equivocal cases were classified as Luminal tumors (Luminal B 52% and A 22%) and harbored mostly at the genomic level chr 17 segmental or large copy number gains. As there is no evidence of benefit of anti-HER2 therapy in these cases, it emphasizes the need of genomic status determination of HER2-equivocal cases.

Legal entity responsible for the study

Anne Vincent-Salomon.

Funding

Has not received any funding.

Disclosure

P. Morel: Full / Part-time employment: Nanostring. H.A. Brauer: Full / Part-time employment: Nanosting. A. Vincent-Salomon: Advisory / Consultancy, Consulting fees: Roche; Advisory / Consultancy, Consulting fees: AstraZeneca; Non-remunerated activity/ies, Contracted Research: Nanostring. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

261P - OncotypeDX® predictive nomogram for recurrence score output: A machine learning system based on quantitative immunochemistry analysis - ADAPTED01 (ID 1096)

Presentation Number
261P
Lecture Time
12:00 - 12:00
Speakers
  • Fabio Marazzi (Roma, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

OncotypeDX (ODX®) can enhance prediction of breast cancer recurrence, guiding adjuvant treatment options. However, the opportunity to access this test is not always possible. The aim of this study is to investigate the correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC) and recurrent score (RS) resulting from ODX®.

Methods

All breast cancer patients who underwent ODX® between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, pathological and IHC features. IHC was performed with standardized quantitative methods. Dataset was split into two subsets (70% for training and 30% for internal validation). Logistic models were built with statistically significant features for predicting RS ≤ 25 or ≤ 20. An external validation set, provided by another center, was used to test reliability of prediction models.

Results

The internal dataset included 407 patients (Table) who underwent ODX®. Mean age was 53.7 (31-80) and 222 patients (54.55%) were > 50 years old. ODX® results showed: 67 patients (16.6%) between 0-10, 272 patients between 11-25 (66.8%) and 68 pts > 26 (16.6%). At the logistic regression analysis, RS score was significantly associated with ER (p = 0.004), PgR (p < 0.001), and Ki67% (p < 0.001) with the threshold equal to 25. Above patients with RS ≤ 25, the generalized linear regression resulted in a well calibrated model with an AUC of 92.2% (sensitivity 84.2%; specificity 80.1%). External validation set included 180 patients and confirmed the model performance with an AUC of 82.3% and good calibration. A nomogram predicting RS score ≤25 was generated.

261P Tumor characteristics training set + internal test set

Training + internal test set – Tumor characteristics
Histological subtype classificationInvasive Ductal Carcinoma318 pts (78,1%)
Invasive Lobular Carcinoma47 pts (11,5%)
Other42 pts (10,3%)
Grading128 pts (6.8%)
2268 pts (65,8%)
3111 pts (27,3%)
pT1a3 pts (0,7%)
1b38 pts (9,3%)
1c216 pts (53,1%)
2143 pts (35,1%)
36 pts (1,5%)
41 pt (0,3%)
pN0233 pts (57,2%)
0i+12 pts (3%)
1mic43 pts (10,6%)
1108 pts (26,5%)
NA11 pts (2,7%)
Mean T diameter [cm]1.9 (Range 0,2-8,5)
Mean Sentinel Lymph Node (SLN) diameter [mm]1.7 (Range 0-40)
Mean Axillary Lymph Node (ALN) diameter [mm]0.8 (Range 0-25)
Mean N Ratio0.14 (0.00 – 1.00)
SLN involvement [n° of nodes]0261 pts (64,1%)
1112 pts (27,5%)
224 pts (5,8%)
31 pt (0,2%)
NA9 pts (2,2%)
ALN involvement [n° of nodes]0338 pts (83%)
 0i+4 pts (1%)
 1mic3 pts (0,7%)
 131 pts (7,6%)
 28 pts (2%)
 35 pts (1,2%)
 51 pt (0,2%)
 NA17 pts (4,1%)
MultifocalityYes97 pts (23,8%)
No300 pts (73,7%)
NA10 pts (2.5%)
MulticentricityYes20 pts (4,9%)
No376 pts (92,4%)
 NA11 pts (2,7%)
PVIAbsent242 pts (59,4%)
Focal51 pts (12,5%)
Moderate32 pts (7,8%)
Massive59 pts (14,5%)
NA23 pts (5,6%)
Mean ER expression87,9% (Range 1-100)
Mean PgR expression62.2% (Range 0-100)
Mean AR expression7.7% (Range 0-90)
Mean Ki67% expression29.8% (Range 0-90)
Her2 Expression0187 pts (46%)
1112 pts (27,5%)
2104 pts (25,5%)
NA4 pts (0,9%)
Fluorescence in situ hybridization (FISH) for HER-2Not determined300 pts (73,7%)
Not amplificated100 pts (23,7%)
Undetermined1 pt (0,2%)
Equivocal1 pt (0,2%)

Conclusions

Quantitative IHC presents a good correlation with RS score in patients with RS ≤ 25, also in external validation set. A nomogram for physician that enhances a cost/effectiveness clinical approach practice has been developed. Prospective clinical application will be tested in further studies.

Legal entity responsible for the study

Fabio Marazzi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

262P - Geriatric parameters predict both disease-related and patient-reported outcomes in older patients with breast cancer (ID 5426)

Presentation Number
262P
Lecture Time
12:00 - 12:00
Speakers
  • Willeke Van der Plas-Krijgsman (Leiden, Netherlands)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The number of elderly breast cancer patients is strongly increasing due to aging. The use of a geriatric assessment in this population has been advocated in many studies and guidelines to identify high risk populations for early mortality and toxicity. Additionally, they could predict relevant outcomes such as quality of life and functional status. This systematic review summarizes all available evidence on predictive factors for disease-specific and patient-reported outcome measures in older patients with breast cancer.

Methods

We performed a systematic review of Pubmed and Embase using keywords “breast cancer”, “prediction” and “elderly” and screened all titles that were published up to June 2017 by two independent reviewers. Papers that investigated the relation between predictive markers (disease-related or patient-related) and disease-specific outcomes, toxicity or patient-reported outcomes (such as quality of life, functional status) were included.

Results

104 papers were included out of 1324 screened titles. Most studies investigated breast cancer-specific outcomes such as survival or recurrence (N = 95). The main predictors were disease-related measurements such as tumor stage or grade. However functional status, cognitive status, comorbidity and gait speed were highly predictive of overall mortality. Treatment toxicity was predicted by age, comorbidity, functional status and polypharmacy. Patient-reported outcomes such as functional status, cognitive decline and emotional functioning were studied in a minority of studies (N = 12) and were predicted by comorbidity, polypharmacy, nutritional and functional status.

Conclusions

This study shows that geriatric parameters can predict survival and patient-reported outcomes in elderly breast cancer patients. This can be used in daily clinical practice to identify patients at risk of early mortality, treatment toxicity or poor functional outcome after treatment. A minority of studies used relevant outcome measures for older patients, showing the need for studies that are tailored for the older population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

263P - Patients with a 21-gene assay in South East London differ from the TAILORx trial population (ID 5865)

Presentation Number
263P
Lecture Time
12:00 - 12:00
Speakers
  • Charalampos Gousis (London, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The 21-gene Breast Recurrence Score® (RS) is an established genomic tool to assess recurrence risk and adjuvant chemotherapy benefit in early breast cancer. The TAILORx study redefined group boundaries of the RS in node negative women. In the 668 patients of the NSABP-B14 study that formed the validation set of the RS younger age was significantly correlated with distant recurrence and tumour size trended toward significance. High tumour grade remained an independent prognostic factor beyond the RS. In the TAILORx study these higher risk groups were under-represented.

Methods

We compared clinical prognostic parameters of women in South East London with available RS with the TAILORx trial population. Retrospective case note analysis of all identified patients between 2013 and 2018 was completed. Women with nodal involvement were excluded. Descriptive statistics were used for comparison with patient characteristics of the TAILORx study.

Results

A total of 269 tests were identified. 42 were excluded for nodal involvement or incomplete clinical data, leaving 227 patients. Differences between the populations are demonstrated for all characteristics and will be presented at the meeting.

263P Patient characteristic

RS<1111-25>26ALL
N (%)34 (11)142 (67)51 (22)227 (100)
Median age (range)48 (28-75)49 (28-74)53 (38-78)50 (28-78)
≤50 yr %56564152
Premenopausal %59644759
Tumour size in cm Median (IQR) Mean (SD)2.0 (1.7-3.0) 2.6 ± 1.52.1 (1.5-3.0) 2.6 ± 1.82.2 (1.6-3.0) 2.4 ± 1.22.1 (1.6-3.0) 2.6 ± 1.6

Tumour grade %

Low

Intermediate

High

6

74

21

4

63

33

0

24

76

4

56

41

Clinical risk %

Low

High

High (TAILORx)

35

65

22

32

68

26

20

80

57

30

70

Conclusions

Our patients have a higher clinical risk than the TAILORx population. They are younger and have larger, higher grade cancers. This population is under-represented in the TAILORx study which was unable to exclude benefit in the ≤ 50 subset and may thus underestimate benefit from chemotherapy in our population. The current RS reporting is biased towards an older, low-risk population.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Gousis: Travel / Accommodation / Expenses: Roche. H. Kristeleit: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Advisory / Consultancy: Roche. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

264P - Predictive tools in adjuvant breast cancer: What is the standard of evidence supporting their utility? A literature review examining validation of Adjuvant!, Cancermath and NHS Predict (ID 1312)

Presentation Number
264P
Lecture Time
12:00 - 12:00
Speakers
  • Alice R. Loft (Christchurch, New Zealand)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Predictive online calculators are used by clinicians as decision aids in early breast cancer (EBC). While use statistics for these calculators have not been published, as of 2017 NHS Predict was being accessed more than 20,000 times a month. These predictive tools have not had accuracy & benefit of use prospectively confirmed in EBC, yet use of calculators has been encouraged in EBC guidelines. It is important to understand the populations informing model development & validation, to understand how data bias may impact predictions in under-represented subpopulations. This work sought to elucidate the risk of bias in model development & validation for 3 online EBC calculators (NHS Predict, Adjuvant! & Cancermath), in an effort to highlight sub-populations where calculated risk & therefore treatment benefit estimates may be less reliable.

Methods

A literature search was conducted in PubMed, search terms were “predict*” “adjuvant” “breast” & “algorithm”. Results were screened for relevance to the three predictive tools under scrutiny & additional references were extracted from relevant papers. Using a modified CHARMS checklist, the relevant sections of the development & validation papers were extracted.

Results

6 development & 24 validation papers were reviewed as summarised in the Table

264P

PredictAdjuvantCancermath
Development population size & date range5694 1977-200837,968 1977-2007499,724 1977-2007
Aged <35 in development population2% (111)0>0.5%
Aged >65 in development population32% (1781)0>17%
Tumour size >5cm in development population5% (287)00
Number of validation studies10133
% retrospective100100100
Total number of patients in validation studies19,86419,61811,203
Age >65 in validations35% (7134)42% (8313)40% (4519)
Age <35 in validations16% (3235)8% (1518)9% (1007)
Tumour size >5cm in validations5% (287)5% (1015)6% (634)
Universal exclusionsMulti-focal, inflammatory, maleMulti-focal, inflammatory, maleMulti-focal, inflammatory, male
Neoadjuvant chemotherapy not an exclusion1 study (121 patients)00
Overall conclusions of validation authorsEarlier versions under-predicted mortality in women <35 Poor performance in tumours >5cm.Poor performance in general in: <35 and >65 More advanced disease Malay ethnicity Overly optimistic survival predictions across subgroups in UK population.Poor performance in < 35 Systematically under-predicted mortality, especially for ER-negative tumours.
.

Conclusions

All 3 predictive tools have under-represented groups in their development cohorts, specifically those under 35 & over 65 years old, as well as larger tumours. Validation studies consistently demonstrate worse performance in these groups. However, due to inconsistent methodology in validation studies, quantitating the summary performance within & across tools is difficult. These predictive tools should be used with caution in under-represented populations. More work is required to look at clinical utility of tools as well as their statistical performance.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

265P - Oncologic outcome of invasive lobular carcinoma: Is it different from that of invasive ductal carcinoma? (ID 2445)

Presentation Number
265P
Lecture Time
12:00 - 12:00
Speakers
  • Hee Jun Choi (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

To evaluate the clinicopathological factors and the oncology outcomes of invasive lobular carcinoma (ILC) patients compared with those of invasive ductal carcinoma (IDC) patients.

Methods

This study was a medical record review based on a prospectively-collected database. We surveyed the clinicopathological characteristics and oncology survival between IDC and ILC following curative surgery at ooo Medical Center between March 2007 and February 2015.

Results

The median follow-up time was 60.5 months (range: 3-121 months). There were 352 breast cancer patients with ILC and 7795 breast cancer patients with IDC. There were 13 breast cancer patients with ILC and 1150 breast cancer patients with IDC in the TNBC patients. The IDC patients had 77.7% of cytokeratin (CK) 5/6 and 86.3% of Epidermal growth factor receptor (EGFR), while ILC patients only had 15.4% of CK5/6 and 23.1% of EGFR. In TNBC, patients with ILC showed a tendency to have a worse prognosis than patients with IDC. However, there was no statistical difference in disease-free survival (DFS, p = 0.122) or overall survival (OS, p = 0.093) between TNBC patients with IDC and with ILC.

Conclusions

Patients with ILC have no different oncologic outcome than patients with IDC. However, patients with ILC in TNBC show a tendency to have a worse prognosis than patients with IDC in TNBC. This result may be related to CK5/6 and EGFR. Further research is needed with larger sample sizes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

266P - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer (ID 2476)

Presentation Number
266P
Lecture Time
12:00 - 12:00
Speakers
  • SERAFIN MORALES Murillo (Lleida, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Nodal involvement is a common prognostic factor in early breast cancer (EBC) but their response and assessment after neoadjuvant chemotherapy (NAC) is controversial, hence its impact in survival is not clear.

Methods

We analyze a cohort of 308 EBC patients with initial nodal involvement and their response to neoadjuvant chemotherapy and their impact in disease free survival (DFS).

Results

Median age was 52 (range 29-87), median tumor size was 38mm (10-100) and 178 patients (57,8%) had initial palpable node involvement. According to the immunohistochemical expression of hormonal receptors, Ki 67 and HER2; 110 patients (35,7%) was HER2 positive, 119 (38,6%) luminal and 79 (25,6%) triple negative breast cancer. After NAC we found a total of pathological complete response in breast (pCRb) of 30% and pathological complete response in axilla (pCRa) of 45%. Response by different subtypes was: in HER2 a pCRb 41,8% and pCRa 56,3%; luminal a pCRb 13% pCRa 30,3% and triple negative a pCRb 41,8% pCRa 50,6%. Luminal patients achieved the worst axillary response (p:0,004) and without other variables with significant association like tumor initial size or palpable axillary nodes. The global coincidence between pCRb and pCRa was 83% and very similar in the different subtypes. Axillary pCR was associated with a better DFS in the global series (HR: 0,377 p:0,000) but not in the luminal patients (HR:0,455 p:0,072) and the median survival in patients with pCRa was 157 months in contrast to 121 in patients that not achieve a pCRa (153 vs 99 in HER2, 160 vs 141 in luminal and 167 vs 93 in triple negative).

Conclusions

The complete pathological response in axila after neoadjuvant chemotherapy is 45% in our serie but lower in luminal patients with only a 30%. There was a high level of concordance between pCR in breast and axilla in all subtypes with an 83%. Achieving pCR in axilla is associated with better disease free survival but this benefit is lower in luminal phenotype.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

267P - Chemotherapy-induced amenorrhea: Prognostic impact on premenopausal Egyptian patients with breast cancer (ID 3761)

Presentation Number
267P
Lecture Time
12:00 - 12:00
Speakers
  • Khaled Abdel Karim (Cairo, Egypt)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer is the second most frequent cancer among women. Disease free survival (DFS) and overall survival (OS) have been improved by different adjuvant chemotherapy regimens; as a consequence, premenopausal patients developed chemotherapy-induced amenorrhea (CIA). Although chemotherapy and ovarian ablation independently improve the outcome of breast cancer, there is controversy about the effect of CIA in these patients. The aim of this study was to analyze the prognostic impact of chemotherapy- induced amenorrhea (CIA) on disease-free survival and overall survival in premenopausal patients with breast cancer following adjuvant chemotherapy.

Methods

Retrospectively, we reviewed the data of 200 premenopausal breast cancer patients, who underwent adjuvant chemotherapy at the Clinical Oncology Department of Ain Shams University, Cairo, Egypt during 2014. The data of one hundred ninety-two patients were analyzed in the study. CIA was defined as the absence of menstruation for a year after the end of chemotherapy. The survival analyses were done using the Kaplan-Meier method and the log Rank Test.

Results

The median follow-up was 4 years. Mean age was 40.8 ± 6 years. CIA occurred in 66.1% of patients. Age and tumor grade were CIA predictors in logistic regression analysis. The 4-year disease-free survival (DFS) was higher in the CIA group than that in the non-CIA group (47.39 months vs 31.80 months, respectively; P = < 0.001), and the 4- year overall survival (OS) was higher in the CIA group than that of the non-CIA group (47.85 months vs 45.296 months, respectively; P = 0.030).

Conclusions

Chemotherapy-induced amenorrhea positively affects disease-free survival and overall survival in the Egyptian premenopausal breast cancer patients treated with adjuvant chemotherapy. It was a better prognostic marker and might be used as a surrogate marker for effective chemotherapy in those patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

Concordance rates between the progesterone receptor isoform ratio determined in core needle biopsy and the corresponding surgical excision in patients with breast cancer. (ID 4448)

Lecture Time
12:00 - 12:00
Speakers
  • Andres M. Elia (Buenos Aires, Argentina)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00
Poster Display session 2 Poster Display session

269P - Predicting the presence of breast cancer using circulating small RNA in the serum (ID 4687)

Presentation Number
269P
Lecture Time
12:00 - 12:00
Speakers
  • Yumiko Koi (Hatsukaichi, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Small RNAs are multiple classes of short non-coding RNAs (ncRNAs) that include microRNAs (miRNAs), transfer RNA fragments (tRFs), and other ncRNA fragments that play essential role in gene regulation. Small RNAs exist in blood circulation within extracellular vesicles (EVs), which have been the center of the attention at cell-to-cell communication tools, or bound to proteins or lipid. Recent studies have shown that the expression levels of small RNAs are different between patients with breast cancer (BC) and cancer-free individuals. Thus, circulating small RNAs have attracted as valuable biomarkers for cancer detection.

Methods

First, we assessed and the expression level of circulating small RNAs in the serum of BC patients (n = 78) and cancer-free volunteers (control) (n = 72) using next generation sequencer. By comparing those expression level, we identified some small RNAs that have signifficant difference between 2 groups as biomarker candidates for BC detection. We constructed a diagnostic model using some small RNAs from biomarker candidates. To test the possibilities that those candidates are released from cancer cells, we next profiled small RNAs within EVs that isolated from the serum of participants in this study and from breast cancer cells (MCF-7 and MDA-MB-231) and normal epithelial cells (184-h TERT).

Results

Twelve circulating small RNAs that expressed significantly higher in BC patients compared to control were identified, indicating potential biomarkers for BC detection. A diagnostic model using 4 small RNAs including isoforms of miRNAs (isomiRs) and tRFs was. The ROC curve analysis revealed that our model showed a high diagnostic accuracy of AUC 0.945 and achieved discriminating stage 0 BCs from control. Importantly, significantly different expression in serum-EVs was observed in 4 small RNAs between BC patients and control. Furthermore, 4 small RNAs were also observed in EVs derived from cell culture media in breast cancer cells and normal epithelial cells and those expressions were aberrant as the same as those of serum-EVs.

Conclusions

These findings suggests circulating small RNAs in serum serve as potential biomarkers for BC detection that enables to include the molecular movement of cancer cells.

Legal entity responsible for the study

Hidetoshi Tahara.

Funding

Has not received any funding.

Disclosure

H. Tahara: Advisory / Consultancy: MiRTeL.

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Poster Display session 2 Poster Display session

270P - Evaluation of germ line mutational status among women with triple-negative breast cancer in Russia (ID 5612)

Presentation Number
270P
Lecture Time
12:00 - 12:00
Speakers
  • Elena Shagimardanova (Kazan, Russian Federation)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Pathogenic germline BRCA1/2 mutations are found in higher rates in patients with triple negative breast cancer (TNBC). As a result, genetic BRCA mutation testing would be beneficial for this particular group of patients. At the same time, it is less clear if mutational burden in other cancer predisposition genes is more frequent in TNBC and has to be recommended for genetic testing. In the current study we aimed to characterize pathogenic germline mutations in TNBC patients fulfilling NCCN criteria of hereditary cancers from Russian Federation.

Methods

Individuals with diagnosis of TNBC were selected to be included in this study according based on the following criteria: (1) young age of disease onset, (2) the presence of relatives with breast or ovarian cancer diagnosis. The NimbleGen SeqCap EZ Choice kit (“Roche”) was used for target enrichment, and sequencing was performed using Illumina MiSeq (“Illumina”). Custom bioinformatic pipeline, including Annovar, HGMD Professional 2017.4 and BIC databases were used to identify pathogenic mutations.

Results

128 patients with triple negative breast cancer aged from 24 to 79 years old were included in this study. 42 woman has their first cancer diagnosis before 40 years old, 77 – between 41 and 60 years old, 9 - were older than 60. 42 patients (33%) carried pathogenic or likely pathogenic variant in BRCA1 gene,10 (8%) in BRCA2 gene and 40 (31%) in one of other genes, including BUB1, CDH1, CDKN2A, CHEK2, EPCAM, FANCI, MLH3, MSH6, PALB2, PMS2, POLE, POLE, RAD50, RBBP8, RET, STK11, APC, ATM, BARD1, BLM. 13 woman had double mutation in two genes, and one patient had double mutation in BRCA1 gene. For the BRCA1 carriers subgroup, the median age at diagnosis was 41(24-64), BRCA2 carriers – 44 (27-62) and other genes carriers – 48 (28-79) year old. Patients with double mutation had median age of cancer manifestation at 42 (32-65).

Conclusions

Approximately 38% of patients with TNBC fulfilling NCCN criteria of hereditary cancer are carriers of pathogenic and likely pathogenic mutations in BRCA1 and BRCA2 genes. And up to 40% - in other cancer susceptibility genes. Thus, the patients with TNBC might be recommended for extended genetic testing depending on age of onset and the presence of a cancer family history.

Legal entity responsible for the study

Tatarstan Cancer Center.

Funding

The work is supported by Russian Foundation for Basic Research № 18-415-160009 and according to the Russian Government Program of Competitive Growth of Kazan Federal University.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

271P - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT) (ID 4142)

Presentation Number
271P
Lecture Time
12:00 - 12:00
Speakers
  • Alberto Ocaña (San Sebastian de los Reyes, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

dNLR is a novel biomarker associated with clinical outcome in solid tumors including early stage breast cancer (BC). Here we report the association of dNLR with pCR in triple-negative (TN) and luminal BC patients (pts) treated with neoadjuvant CT.

Methods

This was a retrospective analysis of two randomized studies (GEICAM/2006-03 - NCT00432172 and ETNA - NCT01822314) involving 821 pts with early stage (>2cm) or locally advanced TN or luminal BC receiving anthracycline/taxane-based CT +/- carboplatin (GEICAM/2006-03) or nab-paclitaxel/paclitaxel followed by anthracycline regimen (ETNA). dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before CT (baseline) and at the end of treatment (EOT). Logistic regression analyses were used to explore dNLR association with pCR at the two time points by molecular subtype.

Results

684 and 137 pts were from ETNA and GEICAM/2006-03 study respectively (TN n = 308; Luminal n = 513). In TN subgroup median baseline dNLR was 1.61 [interquartile range (IQR): 1.25-2.04] and at EOT 1.65 (IQR: 0.96-2.22). In luminal BC median baseline dNLR was 1.68 (IQR: 1.22-1.96) and at EOT 1.48 (IQR: 0.86-1.93). No association with pCR was found in luminal BC. Baseline dNLR was associated with pCR in TNBC in univariate analysis (OR: 0.709, CI: 0.5-1.006, p = 0.0406). At EOT significant association of dNLR as continuous variable with pCR was observed in TNBC both in univariate and multivariate analysis (OR: 0.665, CI: 0.501-0.884, p = 0.0034, n = 255 and OR: 0.62, CI: 0.406-0.946, p = 0.0231, n = 228 respectively). Quartiles distribution of EOT dNLR was also associated with pCR in univariate and multivariate analysis (Q1 vs combined Q2/Q3/Q4 group: OR: 0.32, CI: 0.17-0.64, p = 5e-04 and OR: 0.26, CI: 0.1-0.63, p = 0.002 respectively). Also a ROC curve - based optimal cut off method revealed significant association of EOT dNLR with pCR in TNBC (>2.231, OR: 0.43, CI: 0.25-0.74, p = 0.0035).

Conclusions

No association was found between dNLR and pCR in luminal BC. High dNLR levels at baseline and especially EOT seem to be associated with worse clinical outcome in TN tumors after neoadjuvant CT.

Clinical trial identification

GEICAM/2006-03 - NCT00432172: 07 Feb 2007 ETNA - NCT01822314: 02 Abr 2013.

Legal entity responsible for the study

GEICAM Spanish Breast Cancer Group.

Funding

Has not received any funding.

Disclosure

M. Mansutti: Advisory / Consultancy: Celgene; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca. A. Lluch: Research grant / Funding (self), Research grant / Funding (institution): Amgen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self), Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (self), Research grant / Funding (institution): GSK; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celgene; Research grant / Funding (self), Research grant / Funding (institution): Pierre-Fabre. M. Thill: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genomic Health; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Hexal; Honoraria (self), Travel / Accommodation / Expenses: Medtronic; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Myriad; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PFM Medical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: RTI Surgical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Teva; Advisory / Consultancy, Travel / Accommodation / Expenses: Biom-up; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Neodynamics; Advisory / Consultancy, Travel / Accommodation / Expenses: Norgine; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. L. Gianni: Advisory / Consultancy, MetIS, Novartis, Odonate Therapeutics, Revolution Medicine, Synaffix, Zymeworks: CONSULTANCY: ADC Therapeutics,; Advisory / Consultancy, RESEARCH FUNDING (institution): Zymeworks, Daiichi SankyoZymeworks, Daiichi Sankyo: AstraZeneca; Advisory / Consultancy, PATENTS, ROYALTIES: European Patent Application N. 12195182.6 and 12196177.5’, Roche: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: G1 Therapeutics; Advisory / Consultancy: Genentech; Advisory / Consultancy: Genomic Health; Advisory / Consultancy: MSD; Advisory / Consultancy: Oncolytics Biotech; Advisory / Consultancy: Odonate Therapeutics; Advisory / Consultancy: Onkaido; Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Tahio Pharmaceutical; Advisory / Consultancy: Sandoz; Advisory / Consultancy: SeaGen,; Advisory / Consultancy: Synthon; Advisory / Consultancy: Zymeworks,; Advisory / Consultancy: CD47; Advisory / Consultancy: GENENTA. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

272P - Competing nomogram for late-period breast cancer-specific death in patients with early-stage hormone receptor-positive breast cancer (ID 1733)

Presentation Number
272P
Lecture Time
12:00 - 12:00
Speakers
  • Jianfei Fu (JInhua, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

More than half of early breast cancer recurrences occur after 5 years from the initial diagnosis. An individualized estimate of the risk of late-period breast cancer-specific death (LP-BCSD) after 5 years of endocrine therapy (ET) can improve decision-making for extended endocrine therapy (EET).

Methods

A total of 147,059 eligible patients with breast cancer who survived 5+ years after diagnosis between 1990 and 2007 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses based on the competing risk regression model were used to evaluate predictive factors for high risk of LP-BCSD or LP-non-BCSD. Significant factors were used to build a nomogram to individualize estimates of LP-BCSD or LP-non-BCSD.

Results

The 5- and 10-year LP-BCSD rates were 5.67% and 10.06%, respectively, and the 5- and 10-year LP-non-BCSD rates were 6.72% and 15.50%, respectively. Young age, black race, single marital status, poor differentiation, large tumor size, lymph node metastasis, and ER+/PR- status were independent predictive factors for high risk of LP-BCSD. Age was the most important factor for predicting high risk of LP-non-BCSD. The nomograms, which were based on significant factors identified by the competing risk regression model. A risk score system based on the competing risk nomogram was established to describe the relative risk of LP-BCSD and LP-non-BCSD.

Conclusions

This study explored the novel endpoint of LP-BCSD for further clinical trials. The risk score system is highly useful for patient counseling, especially in discussing EET options with elderly or comorbid patients.

Legal entity responsible for the study

Jianfei Fu.

Funding

Science & Technology Division of Jinhua Zhejiang Province.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

273P - A nomogram to predict pathologic complete response of neoadjuvant chemotherapy in triple-negative breast cancer based on simple blood indicators (ID 1978)

Presentation Number
273P
Lecture Time
12:00 - 12:00
Speakers
  • Fanrong Zhang (Hangzhou, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Triple-negative breast cancer (TNBC) patients who achieve a pathologic complete response (pCR) after Neoadjuvant chemotherapy (NAC) have better prognoses. This study intended to develop an intuitive nomogram based on simple blood indexes to predict the pCR of standard NAC in TNBC patients with an ultimate aim to tailor more beneficial treatments and improve outcomes.

Methods

A total of 80 TNBC patients who received standard NAC, 4 cycles of anthracycline (epirubicin or adriamycin) and cyclophosphamide followed by 4 cycles of taxane, and subsequent surgery in Zhejiang Cancer Hospital between January 2016 and December 2018 were retrospected and their pre-treatment clinical features and several simple blood indexes were collected. The optimal cutoff values of blood indexes were determined by Youden index using the receiver operating characteristic (ROC) curve analysis. The forward stepwise logistic regression (likelihood ratio) analysis was applied to identify predictive factors for pCR of NAC. Then a nomogram was developed according to the logistic model. The calibration of the nomogram was carried out by internal validation with the bootstrap resampling approach and displayed using a calibration curve. The goodness of fit for the model was checked by a Hosmer-Lemeshow test. The discrimination of the nomogram was graphically shown by the ROC curve and quantified by the area under the curve (AUC).

Results

The pCR was achieved in 39 (48.8%) patients after NAC. Multivariate logistic regression analysis identified four independent indicators: clinical tumor stage, lymphocyte monocyte ratio, fibrinogen and D-dimer. The nomogram established based on those factors showed its discrimination with an AUC of 0.803 (95% CI 0.706-0.899) and a bias-corrected AUC of 0.771. The calibration curve and Hosmer-Lemeshow test showed the prediction of the nomogram was a good fit with actual observation.

Conclusions

Based on four simple, easily accessible, inexpensive and objective factors, the nomogram proposed in the present study exhibited a sufficient ability of discrimination for predicting pCR of NAC in TNBC patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

274P - Identification of GSTP1 transferred by extracellular vesicles responsible for adriamycin-resistance in breast cancer cells (ID 3062)

Presentation Number
274P
Lecture Time
12:00 - 12:00
Speakers
  • Sujin Yang (Jiangsu, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Anthracycline/taxane-based chemotherapy is frequently used to treat breast cancer. However, not all patients respond to chemotherapy due to naturalor acquired chemo-resistance. Glutathione S-transferase P1(GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione.

Methods

We identified GSTP1 as a drug-resistance-related factor by microarray. Then, we used cell apoptosis and immunofluorescence staining to confirm the ability of GSTP1-containing exosomes in conferring drug resistance. And the knockdown of GSTP1 gene was performed to found the influence of drug-resistance. Furthermore, the role of GSTP1 and its relationship with exosomes was proved by analysed 40 pairs of breast cancer tissues by IHC. Then, the levels of GSTP1 in serum exosomes were detected in 28 patients treated with neoadjuvant chemotherapy(NAC).

Results

By microarray data, we found that GSTP1, which located in extracellular exosome, is higher in Adriamycin(ADR)-resistant cell line compared with its parental cell line. Then, we also confirmed a higher expression of GSTP1 protein in ADR-resistant cells by immunofluorescence staining and western blot. Moreover, the addition of GSTP1-containing exosomes can increase the resistance to ADR in sensitive cells. Also, we found that a higher expression GSTP1 in the PD/SD group than in the PR/CR group in 40 paired samples collected before and after chemotherapy. Similar results were obtained for the exosomal marker tumor susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. We further explored the levels of GSTP1 in serum exosomes of 28 patients treated with anthracycline/taxane-based NAC, and discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were higher than those in the PR/CR group.

Conclusions

GSTP1-containing exosomes appeared to be essential in conferring resistance to anti-cancer drugs. We explored the predictive role of GSTP1 in circulating exosomes as a biomarker for chemo-sensitivity in patients treated with anthracycline/taxane-based chemotherapy.

Legal entity responsible for the study

Jinhai Tang.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

275P - Expression of x-linked inhibitor of apoptosis protein (XIAP) and its association with clinicopathological parameters in invasive breast cancers (ID 5274)

Presentation Number
275P
Lecture Time
12:00 - 12:00
Speakers
  • Gayathri Devi (Durham, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

XIAP is the most potent inhibitor of both the extrinsic and intrinsic cell death pathways, which is linked to chemotherapy resistance and tumor aggressiveness. We analyzed the correlations between XIAP expression in invasive breast cancers and clinicopathological parameters including metastasis-free survival (MFS) and pathological complete response (pCR) to chemotherapy.

Methods

Breast cancer databases comprising gene expression profiles with clinicopathological annotations from 8,636 non-redundant non-metastatic, non-inflammatory, primary, invasive patients were analyzed for XIAPexpression (binary variable, ”high” vs.“low” by using median as cut-off). XIAP immunohistochemistry was conducted in a cohort of post-chemotherapy mastectomy samples.

Results

High XIAP mRNA expression was associated with pathological ductal type, pT1 tumor size, ER-positive, PR-positive, HR+/HER2-, luminal A and B PAM50 subtypes. Analysis of MFS (3,454 non-stage 4) revealed shorter MFS (p = 8.1E-03, log-rank test) associated with “XIAP-high” group. The hazard ratio for metastatic relapse was 1.20 (95%CI 1.05-1.38, p = 8.17E-03, Wald test) in “XIAP-high” vs.“XIAP-low” group.In multivariate analysis, two variables (GGI and pT) remained significant, whereas the TN subtype and XIAPexpression tended to be (p = 0.059). The prognostic value of XIAPwas significant in the multivariate analysis including two major signatures (70-gene signature, Recurrence Score), suggesting independent prognostic value. The same analysis, but in each molecular subtype separately, showed significant difference in the TN subtype (p = 1.0E-03).Univariate analysis of pCR to anthracycline-based neoadjuvant chemotherapy (1,203 patients) identified 20% pCR in the “XIAP-high” group vs.26% in the “XIAP-low” group (p = 0.015, logit function). Immunohistochemistry revealed high XIAP cytoplasmic staining only in invasive tumors and identified correlates with variables like grade, T, N, M and subtype status.

Conclusions

XIAP-high” tumors are more prone to metastatic relapse and resistance to chemotherapy, suggesting the therapeutic benefit of targeting XIAP in the neoadjuvant setting.

Legal entity responsible for the study

The authors.

Funding

Department of Defense W81XWH-17-1-0297 (to G.R. Devi) and Duke School of Medicine Bridge Fund (to G.R.Devi).

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

276P - The prognostic significance of preoperative tumour marker (CEA, CA15-3) elevation in breast cancer patients (ID 1324)

Presentation Number
276P
Lecture Time
12:00 - 12:00
Speakers
  • Soo Youn Bae (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Tumour markers are widely used for screening and monitoring cancers. CA 15-3 and CEA are FDA-approved tumour markers for monitoring breast cancer. However, the prognostic efficacy of preoperative elevation of CEA and CA15-3 levels in breast cancer remains controversial.

Methods

We retrospectively analyzed the clinicopathological parameters and preoperative serum CEA and CA 15-3 level of 149,238 patients of Korean Breast Cancer Society Registry (KBCSR) Database who underwent surgery between January 2000 and December 2015.

Results

The patients with elevated CA 15-3/CEA level had shown more advanced T stage and N stage, ER negativity, PR negativity and HER2 positivity compared the patients with normal CA15-3/CEA levels. The patients with elevated CA 15-3/CEA level had worse OS than the patients with normal CA 15-3/CEA level. In survival analysis, both elevated group had worst prognosis compared other groups. In subgroup analysis by subtypes, in luminal A, both elevated group had hazard ratio (HR) 2.14 (95% CI 1.01-4.55), only CA 15-3 elevated had HR 2.38 (95% CI 1.58-3.58) and only CEA elevated group had HR 1.79 (95% CI, 1.20-2.68), compared normal group. In luminal B, both elevated group had HR 3.99 (95% CI 2.23-7.16), only CA 15-3 elevated had HR 2.38 (95% CI 1.58-3.58) and only CEA elevated group had HR 1.79 (95% CI, 1.20-2.68), compared normal group. In HER2 subtype group, elevated CEA level was the only independent prognostic factor. However, in TNBC, elevated preoperative CEA and CA 15-3 level were not a significant prognostic factor for OS.

Conclusions

The elevation of preoperative tumor markers was associated with aggressive characteristic and worse overall survival. Preoperative tumor markers predicted the prognosis of the patients and showed differences according to subtypes. In luminal breast cancer, the CA 15-3 elevation has higher hazard ratio than the CEA elevation and the patients with both tumor markers showed the worst prognosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

277P - Correlation of clinical and pathological features with the tumour microenvironment in DCIS: An institutional experience (ID 4877)

Presentation Number
277P
Lecture Time
12:00 - 12:00
Speakers
  • Ann Eapen (Orange, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The predictors of recurrence in ER- DCIS and the role of tumor microenvironment (TME) is unclear. Correlation of clinico-pathologic features of ER- DCIS with molecular markers and PD-L1 expression has not been done. Therefore, we under took this retrospective study comparing the clinical outcomes between ER+ and ER- DCIS and correlated this with the expression of PD-L1 in the tumor cells and the Tumor infiltrating lymphocytes. We hypothesize that increased expression of PD-L1 in ER- DCIS and TILs predict recurrence. The aim of this study was to identify biomarkers in ER- DCIS associated with increased risk of recurrence or progression to metastatic disease.

Methods

50 patients with ER+ and ER- DCIS were identified retrospectively. Clinico-pathologic data was correlated with survival outcomes and local or distant recurrence. Information collected was the size, margin status, nuclear grade, ki-67 expression, architectural pattern, necrosis, and molecular phenotype. 25 cases of ER- DCIS are presented in the abstract. The rest will be presented at the meeting. ER+ and ER- DCIS will be stained for PD-L1, and lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20 for the TILs in ER+ and ER- DCIS. The clinical, radiological and Immuno-pathologic features of ER+ DCIS will be compared with ER negative DCIS.

Results

3/25 (12%) had disease recurrence. Two (67%) had recurrence with metastatic triple negative breast cancer with brain, hepatic and osseous metastasis within 5 years. High grade was associated with the development of systemic disease. 1/3 (33%) had recurrence as ER negative DCIS. 2/3 (67%) had recurrence as ER+ tumor. The rate of recurrence and distant metastasis was seen to be higher in high grade ER negative DCIS.

Conclusions

ER- DCIS has an aggressive phenotype and a distinct biology. It is more likely to present as loco-regional or metastatic disease. Identification of genomic biomarkers, PD-L1 analysis in the tumor and the TILs is currently being undertaken. The molecular drivers and immunologic markers of recurrence in ER negative DCIS continue to be an active area of exploration. Further characterization of ER- DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

278P - Correlation between radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer and pathologic complete response and their impact in recurrence-free survival (ID 2471)

Presentation Number
278P
Lecture Time
12:00 - 12:00
Speakers
  • Ariadna Gasol Cudos (Lleida, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Patients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery and more chemotherapy treatment might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. We investigated the diagnostic accuracy of contrast enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT.

Methods

Patients with EBC, who had undergone CE-MRI before and after NACT, were retrospectively analyzed (n = 421), and regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement.

Results

Overall rCR and pCR rates were 35% (147/421) and 36% (154/421), respectively. We found a total of 70% (101/144) of rCR corresponded to a pCR (meaning the positive predictive value - PPV). In contrast, in 80% (219/272) of patients, residual tumor observed on MRI was pathologically confirmed (meaning the negative predictive value - NPV). Sensitivity to detect a pCR was 65% (101/154), while specificity to detect residual tumor and accuracy were 83% (219/262); and 76% (320/421), respectively. The PPV was significantly lower in luminal compared to HER2 positive and triple negative tumors (10/34 = 29 % vs. 50/62 = 81% and 41/48 = 85% respectively). The concordance between rCR and pCR was moderate (Cohen’s kappa − 0.5) but with low level in luminal tumors (Coheńs Kappa – 0.3). In multivariate analysis both assessments were significantly associated with disease free survival (rCR : HR:0,344 P = 0.001; pCR : HR : 0,154 P = 0.000), but not in luminal tumors (rCR : HR:0,813 P = 0.692; pCR : HR : 0,326 P = 0.275).

Conclusions

The accuracy of preoperative CE-MRI to predict pCR after NACT for EBC is moderate but in luminal tumors did not accurately predict pCR. However, rCR was strongly associated with favorable RFS, especially in HER2 positive and triple negative breast cancer tumors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

279P - Ring-like uptake appearance on dedicated breast positron emission tomography before chemotherapy predicts outcome of neoadjuvant chemotherapy in breast cancer (ID 2632)

Presentation Number
279P
Lecture Time
12:00 - 12:00
Speakers
  • Norio Masumoto (Hiroshima, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Dedicated breast positron emission tomography (DbPET) with 18F-fluorodeoxyglucose (FDG) can detect intratumoral heterogeneity. In a previous study, we proved that intratumoral heterogeneous distribution of FDG on DbPET is significantly related to a high nuclear grade and high Ki-67 proliferation index; we also proved that DbPET is useful for predicting residual breast tumors after neoadjuvant chemotherapy (NAC). This study included patients with breast cancer who exhibited a ring-like uptake without central FDG accumulation on DbPET and aimed to evaluate whether the uptake can predict the effects of NAC in patients with breast cancer.

Methods

The study included 83 consecutive patients with breast cancer who subsequently underwent DbPET and NAC between August 2016 and March 2019 and evaluated the relationship between pathological response to NAC and clinicopathologic factors (clinical T1: n = 14; clinical N0: n = 33; nuclear grade 1 or 2: n = 22; Ki67 ≥ 20: n = 78; ER positive: n = 52; and HER-2 positive: n = 32), such as intratumoral heterogeneous distribution of FDG (positive: n = 54) and ring-like uptake without central FDG accumulation (positive: n = 11) on DbPET images.

Results

Surgical pathological findings obtained after the NAC indicated pathological complete response (pCR) and non-pCR in 32 (38.6%) and 51 (61.4%) patients, respectively. For all the patients, significant predictors for pCR were identified in univariate analyses (clinical T: odds ratio = 3.60, p = 0.03; clinical N: odds ratio = 2.48, p = 0.049; HER-2 overexpression: odds ratio = 2.72, p = 0.03; and ring-like uptake: odds ratio = 5.33, p = 0.01) and multivariate analyses (HER-2 overexpression: odds ratio = 3.29, p = 0.03; ring-like uptake: odds ratio = 17.6, p = 0.0006) (Table).

279P Univariate and multivariate logistic analysis of significant predictive clinicopathological factors for pCR

CharacteristicUnivariate logistic analysis
Multivariate logistic analysis
OR95%CIpOR95%CIp
Age, <50 v ≥ 501.380.57-3.380.481.970.65-5.980.23
Clinical T, T1 v T2- T43.601.11-12.90.033.860.97-15.40.06
Clinical N, Negative v Positive2.481.00-6.280.0492.860.97-8.420.06
Nuclear Grade, 3 v 1-21.490.54-4.380.451.650.41-6.700.48
Ki67, ≥20 v < 202.640.37-52.80.361.340.11-16.50.82
ER, Negative v Positive1.250.50-3.120.631.050.33-3.340.93
HER-2, Positive v Negative2.721.09-6.940.033.29 1.11-9.730.03
Intratumoral heterogenity, Positive v Negative1.500.59-3.780.391.690.43-6.570.45
Ring-like uptake, Positive v Negative5.331.40-26.10.0117.62.27-136.20.006

Conclusions

Ring-like uptake on DbPET provides predictive value for evaluating pCR to NAC in patients with breast cancer and might inform therapeutic decisions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

280P - Defining a SUV decrease cut-off in PET/CT response monitoring after one cycle of preoperative breast cancer chemotherapy (ID 3911)

Presentation Number
280P
Lecture Time
12:00 - 12:00
Speakers
  • Marcin Kubeczko (Gliwice, Poland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

A decrease in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer.

Methods

We reviewed the records of patients enrolled to the prospective study of prediction of preoperative chemotherapy response (MILESTONE-BreastPred). In the whole group PET/CT was used as an initial method of staging and as response assessment after 1st cycle of chemotherapy. We analysed data of 425 patients, 19.8% TNBC, 12.2% nonluminal HER2-positive and 68% luminal cancers. 88% of patients were stage II or III. pCR rate was 24.8% (ypT0/is ypN0). 31.1% of patients showed progressive disease during follow-up. The aim of the study was to assess the clinical utility of various cut-offs of SUVmax decrease to predict both pCR and disease relapse.

Results

We analysed SUVmax decrease cut-off of 20%, 30%, 40%, 50 and 60%. For pCR prediction, the sensititivity was above 50% for cut-offs 20%-40%, while specificity exceeded 50% for cut-off values 40-60%. In the whole range of cut-offs, there was highly statistically significant difference in pCR rate between low and high SUVmax decrease (p < 0.001). Cut-off of 40% was chosen, providing optimal trade-off between sensitivity and specificity with positive likelihood ratio 1.89, negative likelihood ratio 0.49, PPV 38.4% and PPV 86.0%. Prediction of disease relapse based on 1st cycle SUVmax decrease was more challenging, with sensitivity above 50% for cut-offs 20-30% and specificity above 50% for cut-offs 40-60%. For cut-off 40% the difference in disease relapse between groups was closest to the limit of statistical significance (p = 0.085) and provided PLR 0.81, NLR 1.17, PPV 26.6% and NPV 65.6%.

Conclusions

Prediction of pCR by 1st cycle SUVmax decrease was feasible, with good balance of specificity and sensitivity for cut-off 40%. This cut-off provides the most prominent, although not significant in this analysis, association with the risk of disease relapse. The study was supported by the Polish National Center of Research and Development MILESTONE project–Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no.STRATEGMED2/267398/4/NCBR/2015.

Legal entity responsible for the study

The authors.

Funding

The study was supported by the Polish National Center of Research and Development MILESTONE project – Molecular diagnostics and imaging in individualized therapy for breast, thyroid and prostate cancer, grant no. STRATEGMED 2/267398/4/NCBR/2015.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

281P - Effect of thioredoxin 1 quantity detection to complement the mammography in breast cancer diagnosis (ID 1849)

Presentation Number
281P
Lecture Time
12:00 - 12:00
Speakers
  • Younju Lee (Daejeon, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer is one of the leading cancers for women worldwide. Mammography is the most widely used to screen breast cancer, although it is inaccurate in young women or women with dense breasts in Korea and Asian countries. Since tumor cells are often under extremely high oxidative or hypoxia, it is widely accepted that Trx1 express high level in malignant cells. Trx1 as a biomarker in blood for breast cancer detection by studies of Trx1 gene and protein expression differences in many malignant tissues and bloods from various cancer patients. It has been shown that gene expression level of Trx1 was the highest in breast cancer tissue among many different cancers in contrast to the lowest in normal breast tissue. Therefore, it would be interesting to examine whether the quantitation of Trx1 from blood could be a tool to detect breast cancer and to complement mammography.

Methods

We have developed an ELISA kit quantitating Trx1. Trx1 levels of bloods from 116 normal healthy women, 140 confirmed breast cancer patients with stage from 0 to 4, and each 30 confirmed patients of lung, ovarian, gastric, colorectal, and cervical cancer have been estimated by the kit. The test results were analyzed by ROC curve, one-way ANOVA test, and unpaired t-test.

Results

The mean value of Trx1 level from normal women was 7.506 (U/mL) and that from breast cancer patients was 37.75. The Trx1 level clearly differentiated breast cancers from normal cases with sensitivity of 96.4% and specificity of 99.1% (AUC 0.990, p < 0.001). Each level of Trx1 from lung (16.7), ovarian (15.50), gastric (15.66), colorectal (16.39), and cervical (22.51) cancer was below the cut-off value (22.8 U/mL) for breast cancer detection. We compared normal women to breast cancer patients’ Trx1 levels and BI-RADS categories. Among the normal women, the false positive rate of mammography was 26% whereas that of Trx1 quantitation was 1%. Among the breast cancer patients, the false negative rate of mammography was 24.82% and that of Trx1 quantitation was 3.76%.

Conclusions

These results indicated that the blood level of Trx1 quantitation estimated by the ELISA kit could be an effective and specific modality to detect breast cancer from blood and also could complement current limits of mammography for small and dense breasts.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

282P - Identification of ultralow risk breast cancer patients (probable overdiagnosis) (ID 2221)

Presentation Number
282P
Lecture Time
12:00 - 12:00
Speakers
  • Salvador Gamez Casado (Cadiz, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The universalisation of mammographic screening has caused an increase in ultralow risk breast cancer diagnosis. Identifying subgroups with no events related to mortality due to breast cancer in the long term (overdiagnosis) may be useful so as not to subject them to unnecessary treatment (overtreatment).

Methods

New ultralow risk criteria are described by means of mammographic screening diagnosis, tumour palpability, tumour phenotype, and absence of axillary node involvement. We identified patients with no events related to breast cancer mortality through a descriptive, observational, and retrospective study.

Results

Among the 746 patients with stage I and IIA breast cancer attended between 1/1/2001 and 31/12/2014, 110 (14.75%) came from mammographic screening with non-palpable tumours. The median age was 58 years old (38-71). 88 (80%) were hormone receptor positive (HR+), 10 (9.10%) were triple negatives, and 11 (10%) were HER-2. The median follow-up was 10 years (3.5-17). Only 3 patients developed metastasis, there were no loco-regional recurrence, 7 showed second primary tumours, and there were 4 deaths, 2 due to breast cancer and 2 due to other reasons. Overall survival (OS) was 92.80%, disease-free survival (DFS) was 85.20%, and the distant metastasis-free interval (DMFI) was 95.60%. In 88 patients with HR+ tumours, OS was 95.7%, DFS was 86.50%, and DMFI was 96.30%. In 34 (38.60%) histological grade 1 HR+ tumours (probably Luminal A), and in 54 (61.40%) histological grade 2-3 HR+ tumours (probably Luminal B), OS was 93.80% and 96.90% (p = 0.669), DFS was 81.90% and 89.30% (p = 0.400), and DMFI was 100% and 94.40% (p = 0.307). In triple negatives, OS was 85.70%, DFS 77.10%, and DMFI was 100%. In subgroup HER-2, there were no events. In tumours smaller and larger than 1 cm, OS was 100% and 90.20% (p = 0.168), DFS was 93.20% and 84.10% (p = 0.742), and DMFI was 100% and 95.50% (p = 0.296).

Conclusions

Patients with non-palpable tumours detected in mammographic screening have an ultralow risk. The absence of events related to breast cancer mortality makes them candidates for overdiagnosis. De-escalation of treatment should be considered. The authors will incorporate genomic risk to optimise the identification of overdiagnosis.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

283P - Prevalence of vitamin D3 deficiency among women with early breast cancer receiving chemotherapy in an oncology dayward (ID 5291)

Presentation Number
283P
Lecture Time
12:00 - 12:00
Speakers
  • Warner Finstad (Cork, Ireland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The Irish Longitudinal Study on Ageing (TILDA) estimates that 13.1% of the Irish population is vitamin D3 deficient, compared with less than 6% of the US population surveyed in the National Health and Nutrition Examination Survey (NHANES). In recent years, numerous studies have shed light on a potential role for vitamin D3 in breast cancer risk modification and prognosis. We set out to assess the prevalence and clinical significance of vitamin D3 deficiency in women with breast cancer receiving chemotherapy in an Irish oncology dayward.

Methods

Retrospective chart review was conducted to collect data incuding patient age, cancer stage at diagnosis, date of treatment initiation and 25-hydroxy vitamin D3 (25(OH)D3) levels at start of treatment. Vitamin D3 deficiency was defined as a value <50 nmol/L. Charlson Comorbidity Index (CCI) was caluclated for all patients. Mean 25(OH)D3 levels by season (autumn, winter, spring, summer) were also caluclated. As the data set was not normally distributed, inter-group comparison was conducted using the Kruskal-Wallis Test with p < 0.05 considered significant.

Results

41 women had available baseline 25(OH)D3 levels and were included. 66% were deficient in 25(OH)D3 at baseline. The prevalence of vitamin D3 deficiency showed substantial seasonal variation, being highest in the winter months (88%) and lowest in the summer months (0%). Furthermore, mean 25(OH)D3 levels were lowest in the winter months (29.0nmol/L + 13.8) and highest in the summer months (66.3nmol/L + 11.5). The difference in mean 25(OH)D3 levels across the four seasons was significant (p = 0.022). Women who were deficient in vitamin D3 tended to be younger (p = 0.00001), have a higher cancer stage (p = 0.0071), and have a less favorable 10-year all cause mortality risk as indicated by their CCI (p = 0.0041).

Conclusions

We found a striking prevalence of 25(OH)D3 deficiency among women with breast cancer receiving adjuvant/neoadjuvant chemotherapy in an Irish oncology dayward. Notable seasonal variation in mean vitamin D3 levels was observed. Vitamin D3 deficiency was found to be more prevalent in younger women and was associated with a higher stage of breast cancer as well as a less favorable 10-year all cause mortality risk.

Legal entity responsible for the study

the authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

284P - Changes in ER pathway activity score during neoadjuvant letrozole to assess therapy response and predict disease free survival (DFS) in ER positive breast cancer patients (ID 4247)

Presentation Number
284P
Lecture Time
12:00 - 12:00
Speakers
  • Arran K. Turnbull (Edinburgh, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Despite ER positive IHC staining, some patients do not respond to neoadjuvant endocrine therapy, suggesting that ER staining lacks specificity to predict response. We developed a method to infer a quantitative signal transduction pathway activity score (PAS) from mRNA levels (microarray, qPCR) of pathway-associated transcription factor target genes. Initial studies suggest that ER PAS may have higher specificity than ER IHC in predicting endocrine therapy response. In this study, we correlated pre-treatment ER PAS and changes in ER PAS during neoadjuvant letrozole treatment to therapy response and DFS.

Methods

We collected fresh frozen RNA from tumor samples of 30 ER IHC positive post-menopausal patients with primary localized breast cancer, treated with neoadjuvant letrozole at Edinburgh Western General. In total, 30 pre, 25 mid (median 27 days), and 29 post-treatment (median 136 days) samples were analysed. Clinical outcome was assessed (RECIST, n = 29) at circa 3 months treatment by 3D ultrasound, with 1 complete (CR), 21 partial responses (PR), 2 stable (SD), and 5 progressive diseases (PD). Using RT-qPCR, target gene expression was measured for ER, androgen receptor, PI3K, Hedgehog, TGFβ and Wnt pathways. PAS were expressed on a normalized scale (0 to 100).

Results

Pre-treatment ER PAS was significantly higher in responders (CR/PR) than non-responders (SD/PD), PAS=45 vs 24, respectively, T-test p = 0.01. Pre-treatment ER PAS correlated with decrease in ER PAS during treatment (cor=0.87 and 0.7, mid and-post treatment, respectively). At mid-treatment, ER PAS of responders had decreased to PAS of non-responders (20 vs 19, respectively), remaining low during further treatment. Decrease in ER PAS was significantly higher in responders (-30) than non-responders (-6), p = 0.01. Higher ER PAS after treatment correlated to shorter DFS (COX proportional hazards p = 0.02). Baseline PAS of other pathways did not correlate with response, but changed significantly during treatment.

Conclusions

This study confirms that ER PAS in ER-positive patients, measured before and after neoadjuvant endocrine therapy, has potential to predict and assess therapy response, and predict DFS.

Legal entity responsible for the study

Philips Electronics Nederland B.V., acting through its HealthWorks Molecular Pathway Dx.

Funding

Has not received any funding.

Disclosure

M. A. Inda: Full / Part-time employment: Philips Reseach. A. van de Stolpe: Full / Part-time employment, has Philips stocks: Philips Research. D. Keizer: Full / Part-time employment: Philips. D. Clout: Full / Part-time employment: Philips Reasearch. H. van Zon: Full / Part-time employment: Philips Reasearch. M. Akse: Full / Part-time employment: Philips. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

285P - Second primary malignancies in patients with breast cancer (ID 568)

Presentation Number
285P
Lecture Time
12:00 - 12:00
Speakers
  • Carlos Erasun Lecuona (Barcelona, Barcelona, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The risk of developing second primary malignancies (SPM) in patients (p) with breast cancer (BC) is higher than among the general population. Tamoxifen, chemotherapy and breast irradiation are associated with an increased risk of SPM. The aim of this study was to investigate the clinicopathological characteristics of the non BC SPM in p with primary diagnostic of BC.

Methods

We conducted a retrospective study in a cohort of 2,111 women with BC diagnosed between 1975 and 2014 in a regional cancer institute in Spain. We evaluated the incidence and pattern of SPM per Warren and Gates criteria, and the impact of breast cancer treatment on SPM.

Results

57p (2.7%) of the cohort developed a SPM, 13 of them (23%) had synchronous tumors and 44p (77%) had metachronous tumors. 10p (18%) developed a third primary malignancy and 1p (1.7%) developed a fourth primary malignancy. The most frequent SPM were hematological malignancies (HM) (11p, 19%), followed by endometrial (7p, 12.3%), gastric (7p, 12.3%), lung (6p, 10.5%), parotid tumors (6p, 10.5%) and melanoma (6p, 10.5%). The mean latency period for SPM was 62.7 months. HM were developed in 0.52% of the cohort of 2,111p. Myeloid neoplasms were diagnosed in 6p (0.28%). Among them, 1p developed chronic myeloid leukemia and 5p developed myelodysplastic syndromes (MDS), including refractory anemia with excess blasts-2 (2p) and 5q minus syndrome (2p). Lymphoid neoplasms were diagnosed in 5p (0.24%). The incidence of HM was similar in both anthracycline-treated and not treated p (0.48% and 0.58%, respectively). The incidence of HM in p treated with radiotherapy was higher than in p who did not receive radiotherapy (0.65% vs 0.19%).

Conclusions

HM are the most frequent non BC SPM in p treated from BC; frequently they are therapy related neoplasms. Deescalating chemotherapy and radiotherapy in BC and finding genetic markers of early malignancy detection are mandatory.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

286TiP - Phase II randomized trial of neoadjuvant trastuzumab and pertuzumab (TP) with either palbociclib + letrozole (Pal+L) or paclitaxel (Pac) for elderly patients with estrogen receptor & HER2 positive (ER+/HER2+) breast cancer (BC) (International Breast Cancer Study Group IBCSG 55-17, TOUCH) (ID 1428)

Presentation Number
286TiP
Lecture Time
12:00 - 12:00
Speakers
  • Laura Biganzoli (Prato, Italy)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

HER2 blockade in combination with chemotherapy (CT) remains the treatment of choice for patients with early HER2+ BC, irrespective of ER status. Patients with HER2+ early BC co-expressing ER may benefit from HER2 blockade in combination with endocrine therapy (ET) and new targeted agents. Elderly patients benefit from HER2 blockade as much as younger ones but they have higher risks of adverse events, mostly induced by the CT partner, making de-escalation of CT appealing. Recent data have elucidated cyclin-dependent kinases 4 and 6 (CDK4/6) as key therapeutic targets functioning downstream of both ER and HER2 pathways suggesting CDK4/6 inhibitors like Pal may be ideal partners for ET in this context. Pre-clinical and clinical data suggest that a gene signature of functional loss of Retinoblastoma (RBsig) might predict sensitivity to CT vs CDK4/6i in ER+/HER2+ early BC. The TOUCH hypothesis is that neoadjuvant therapy with Pal + ET + dual HER2 blockade may be more active in patients with ER+/HER2+ RBsig LOW early BC while those with RBsig HIGH may require CT.

Trial design

TOUCH is an open-label, multicenter, randomized phase 2 neoadjuvant trial. 144 patients ≥65 years with ER+/HER2+ primary BC will be randomized (1:1) to dual HER2 blockade (5 doses T+P) + either Pal (125 mg/d po; 21 of 28d x 4 cycles) + L (daily x 16 weeks), or Pac (80 mg/m2 iv, d1,8,15 q28 days x 4 cycles), before surgery. RBsig (HIGH vs LOW) will be determined centrally on mandatory pre-treatment biopsies. Baseline geriatric assessment includes G8, Instrumental Activity of Daily Living, Charlson comorbidity index. The primary objective is to explore the interaction between RBsig and treatment activity assessed by pathological complete response (pCR). Exact logistic regression will test RBsig by treatment interaction (2-sided a=.05) and estimate odds ratios (OR) for pCR. The sample size provides 86% power, assuming an overall pCR rate of 26%, and OR = 2.4 vs OR = 0.11 for RBsig LOW vs HIGH. Accrual began April 2019.

Clinical trial identification

NCT03644186.

Legal entity responsible for the study

International Breast Cancer Study Group.

Funding

Pfizer, Roche.

Disclosure

L. Biganzoli: Advisory / Consultancy, consultant and in an advisory role: AstraZeneca; Advisory / Consultancy, consultant and in an advisory role: Celgene; Advisory / Consultancy, consultant and in an advisory role: Eisai; Advisory / Consultancy, consultant and in an advisory role: Genomic Health; Advisory / Consultancy, consultant and in an advisory role: Ipsen; Advisory / Consultancy, consultant and in an advisory role: Lilly; Advisory / Consultancy, consultant and in an advisory role: Novartis; Advisory / Consultancy, consultant and in an advisory role: Pfizer; Advisory / Consultancy, consultant and in an advisory role: Pierre Fabre; Advisory / Consultancy, consultant and in an advisory role: Roche; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Genomic Health; Research grant / Funding (institution): Novartis. E. Brain: Honoraria (self), receipt of honoraria or consultation fees: Roche; Honoraria (self), receipt of honoraria or consultation fees: Pfizer; Honoraria (self), receipt of honoraria or consultation fees: AstraZeneca; Honoraria (self), receipt of honoraria or consultation fees: BMS; Honoraria (self), receipt of honoraria or consultation fees: Celgene; Honoraria (self), receipt of honoraria or consultation fees: Clinigen; Honoraria (self), receipt of honoraria or consultation fees: Hospira; Honoraria (self), receipt of honoraria or consultation fees: Janssen; Honoraria (self), receipt of honoraria or consultation fees: Mylan; Honoraria (self), receipt of honoraria or consultation fees: OBI Pharma; Honoraria (self), receipt of honoraria or consultation fees: Puma; Honoraria (self), receipt of honoraria or consultation fees: Samsung. L. Malorni: Research grant / Funding (self), research funding and consulting fees: Pfizer. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

287TiP - Neoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): An open label randomized phase II trial (ID 1479)

Presentation Number
287TiP
Lecture Time
12:00 - 12:00
Speakers
  • Heather L. McArthur (Los Angeles, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) is safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, HER2-directed therapy with ICI administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic backbones; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). This randomized, multicenter, phase II, open-label trial, will evaluate the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K (NCT03747120).

Trial design

174 patients (pts) ≥18y with previously untreated, clinical stage II-III, HER2+ breast cancer will be randomized 1:1:1 to one of the 3 arms, stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive THP: T at 80 mg/m2 weekly for 12 weeks, H day 1 at 8 mg/Kg (loading dose) and then 6 mg/Kg every 3 weeks x 3 doses, P day 1 at 840 mg (loading dose) and then 420 mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K day 1 at 200mg (flat dose) and then every 3 weeks x 3 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose of T. After surgery, pts are treated per the treating physician’s discretion including HER2-directed therapy and radiotherapy per local clinical standards. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity.

Clinical trial identification

NCT03747120.

Legal entity responsible for the study

The authors.

Funding

Breast Cancer Research Foundation, Merck & Co.

Disclosure

H.L. McArthur: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Genomic Health; Research grant / Funding (institution): ZIOPHARM Oncology; Travel / Accommodation / Expenses: Puma Biotechnology. J.H.S. Leal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca. D.B. Page: Honoraria (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dohme; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nektar; Advisory / Consultancy: NanoString Technologies; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Speaker Bureau / Expert testimony: Philips Healthcare. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Radius Health; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Advisory / Consultancy, Research grant / Funding (institution): Biothernostics Inc.; Advisory / Consultancy: Spectrum Pharma; Advisory / Consultancy: Taiho; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Daiichi Pharma. L. Spring: Advisory / Consultancy: Novartis; Advisory / Consultancy: Lumicell; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Research grant / Funding (institution): Tesaro. R.K. Basho: Advisory / Consultancy: Puma Biotech; Advisory / Consultancy: Heron Therapeutics. S. Verma: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Puma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Mylan. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

288TiP - A randomized phase II study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy (ID 1481)

Presentation Number
288TiP
Lecture Time
12:00 - 12:00
Speakers
  • Heather L. McArthur (Los Angeles, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this randomized phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo/cryo versus standard care in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse (NCT03546686).

Trial design

Eligible pts are ≥18y, with ER < 10%, PR < 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 160 pts will be randomized to one of two arms: definitive breast surgery (control arm) or ipi/nivo/cryo followed by breast surgery and adjuvant nivo (intervention arm). Pts in the intervention arm will undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts in the intervention arm will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all study patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status at study entry (positive versus negative). The primary endpoint is 3-year event free survival (EFS). Secondary endpoints include invasive disease-free survival (iDFS), distant disease-free survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore potential predictors of efficacy and toxicity.

Clinical trial identification

NCT03546686.

Legal entity responsible for the study

The authors.

Funding

Susan G. Komen, Bristol-Meyers Squibb, BTG International Ltd., Breast Cancer Research Foundation, ASCO Advanced Clinical Research Award.

Disclosure

H.L. McArthur: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Spectrum Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Genomic Health; Research grant / Funding (institution): ZIOPHARM Oncology; Travel / Accommodation / Expenses: Puma Biotechnology. E.A. Comen: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Henron Therapeutics. S.B. Solomon: Advisory / Consultancy: BTG; Advisory / Consultancy: Johnson & Johnson; Advisory / Consultancy: Adgero; Advisory / Consultancy: Aperture Medical; Advisory / Consultancy: Xact Robotics; Advisory / Consultancy: Innoblative Designs; Shareholder / Stockholder / Stock options: Immunomedics; Shareholder / Stockholder / Stock options: Aspire Bariatrics; Shareholder / Stockholder / Stock options: Aperture Medical; Shareholder / Stockholder / Stock options: Johnson & Johnson; Shareholder / Stockholder / Stock options: Motus GI; Shareholder / Stockholder / Stock options: Progenics; Research grant / Funding (institution): Johnson & Johnson; Research grant / Funding (institution): Elesta; Research grant / Funding (institution): AngioDynamics; Research grant / Funding (institution): GE Healthcare. J.H.S. Leal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca. D.B. Page: Honoraria (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Merck Sharpe & Dohme; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nektar; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Puma Biotechnology; Speaker Bureau / Expert testimony: Genentech/Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: MedImmune; Speaker Bureau / Expert testimony: Philips Healthcare. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

289TiP - ALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer (ID 4334)

Presentation Number
289TiP
Lecture Time
12:00 - 12:00
Speakers
  • Michail Ignatiadis (Brussels, Belgium)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Early stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. On March 8th 2019, the Food and Drug Administration approved anti–PD-L1 antibody, atezolizumab, in combination with chemotherapy for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. ALEXANDRA/IMpassion030 is a global, prospective, randomized, open-label, phase 3 trial currently investigating the efficacy, safety and pharmacokinetic profile of adjuvant atezolizumab plus standard anthracycline/taxane adjuvant chemotherapy versus chemotherapy alone in early stage TNBC.

Trial design

ALEXANDRA/IMpassion030 will randomize 2300 patients with operable stage II-III TNBC, confirmed by central pathology review. Patients are stratified by type of surgery, nodal status, and centrally assessed PD-L1 status. Adjuvant chemotherapy consist of weekly paclitaxel 80 mg/m2 for 12 weeks followed by dose dense anthracycline (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2) and cyclophosphamide 600 mg/m2 for 4 doses every 2 weeks or the same chemotherapy regimen (T-EC/AC) given concomitantly with atezolizumab 840 mg every 2 weeks followed by maintenance atezolizumab 1200 mg every 3 weeks until completion of 1 year of atezolizumab. The primary end-point is invasive disease-free survival (iDFS) and secondary end-points include iDFS by PD-L1 and lymph node status, overall survival, safety, patient functioning and health related quality of life (HRQoL). Tumor tissue and blood samples will be collected for biomarker research. The first site was activated May 4th 2018, and approximately 430 sites are expected to open globally in 30 countries. This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials.

Clinical trial identification

NCT03498716.

Legal entity responsible for the study

This trial is sponsored by Roche and conducted in partnership with the Breast International Group, Frontier Science and Technology Research Foundation, Institute Jules Bordet and Alliance Foundation Trials.

Funding

Roche.

Disclosure

M. Ignatiadis: Advisory / Consultancy: Celgene, Novartis, Pfizer, Seattle Genetics, Tesaro; Research grant / Funding (institution): Roche, Menarini Silicon Biosystems, Janssen Diagnostics, Pfizer; Travel / Accommodation / Expenses: Pfizer,Bayer. H.L. McArthur: Advisory / Consultancy: LIlly, Amgen, Immunomedics, Pfizer, Genentech, BMS, Genomic Health, Merck, spectrum pharmaceuticals; Research grant / Funding (institution): BMS, Lilly, Merck, Ziopharm Oncology. J. Martinez: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. C. Lai: Full / Part-time employment: Roche/Genentech; Shareholder / Stockholder / Stock options: Roche/Genentech. T. Goulioti: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.; Shareholder / Stockholder / Stock options: GlaxoSmithKline; Spouse / Financial dependant: GlaxoSmithKline, UCB. A. Bouhlel: Full / Part-time employment: Roche. V. Balta: Research grant / Funding (institution): AstraZeneca, Roche/Genentech, Pfizer, Novartis, Tesaro, Servier, GlaxoSmithKline.. G. Viale: Honoraria (self): MSD Oncology; Advisory / Consultancy: Dako, Roche/genentech, Astellas Pharma, Novartis; Research grant / Funding (self): Roche/genentech; Research grant / Funding (institution): Ventana Medical Systems, Dako/Agilent Technologies; Travel / Accommodation / Expenses: Roche, Celgene. D.A. Nguyen: Shareholder / Stockholder / Stock options: Roche/Genentech; Full / Part-time employment: Roche/Genentech. R.D. Gelber: Research grant / Funding (institution): Roche, Novartis, Pfizer, Merck, Celgene, Ferring, Ipsen, AstraZeneca. M. Piccart: Officer / Board of Directors: Radius; Advisory / Consultancy: AstraZeneca, Lilly, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Camel-IDS, Crescendo Biologics, Periphagen, Huya, Debiopharm, PharmaMar, G1 Therapeutics, Menarini, Seattle Genetics, Immunomedics, Oncolytics; Research grant / Funding (institution): AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche-Genentech, Synthon, Radius, Servier. E.P. Winer: Honoraria (self): Genentech, Leap, Carrick Therapeutics, Lilly, Seattle Genetics, GSK. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

290TiP - Role of individualized intervention(s) on quality of life (QoL) and adherence to adjuvant endocrine therapy in premenopausal women with early-stage breast cancer (bc): MyChoice study (ID 2107)

Presentation Number
290TiP
Lecture Time
12:00 - 12:00
Speakers
  • Shahid Ahmed (Saskatoon, Canada)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Combination of an aromatase inhibitor and ovarian suppression is more effective than tamoxifen alone in premenopausal women with high risk ER or PR positive BC. However, combination therapy has been associated with more adverse effects, poor treatment adherence, and decline in QOL. Various behavioral interventions can be effective to reduce treatment-related side effects and thereby to improve treatment tolerance and QOL. Nevertheless, there is a paucity of evidence about effect of individualized behavioral and complementary interventions in younger women who are treated with combination endocrine therapy. The study aims to evaluate if younger women with early stage BC treated with combination endocrine therapy could benefit from individualized behavioral and complementary intervention (s) during their treatment. This benefit will be assessed primarily by change in QOL and cognitive function from the baseline measurement and secondarily by adherence to adjuvant endocrine treatment.

Trial design

In this phase 2 multicenter study 40 premenopausal women with stage I, II and III ER/PR positive BC treated with combination endocrine therapy are being recruited. All participants will be provided a list of behavioral interventions such as exercise, yoga, acupuncture, and massage therapy. A participant will be able to select one or more intervention based on her preferences. Assessments of patients reported outcomes will be performed at baseline, at 3, and every 6 months, thereafter for up to 3 years. The QOL and cognitive function will be assessed using Functional Assessment of Cancer Therapy – Breast Symptom Index (FACT-B), FACT – Endocrine System (FACT-ES), and FACT-Cognitive Function scales. Linear mixed models will be used to assess changes over time for overall QOL and for separate components of QOL. Treatment adherence will be monitored monthly basis. Individually-tailored behavioral and complementary interventions could promote self-management and empower the women with early stage BC to manage treatment related side effects.

Clinical trial identification

NCT03407768.

Legal entity responsible for the study

Shahid Ahmed.

Funding

College of Medicine, University of Saskatchewan.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

291TiP - Correlation between the density of tumour-infiltrating lymphocytes, immune cell subsets in tumour stroma and response to systemic therapy in breast cancer (ID 5812)

Presentation Number
291TiP
Lecture Time
12:00 - 12:00
Speakers
  • Cvetka Grasic Kuhar (Ljubljana, Slovenia)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The density of tumor-infiltrating lymphocytes (TIL) is a predictive factor for response to neoadjuvant systemic therapy (NAST) in breast cancer. High TIL density correlates with higher complete pathologic remission (pCR) in triple negative and HER2 positive breast cancer. Additionally, not only TIL density but also subsets of immune cells in tumor stroma seem to play an important role in cancer and immune cell interaction and response to chemotherapy. Our aim is to determine TIL density and expression of CD 20, CD3, CD8, PD-L1, FOXP3 and PGM1 on core biopsy specimen and find a correlation with pCR.

Trial design

We will conduct a prospective study on early breast cancer patients (n = 180) treated with NAST. Patients with breast tumor >2 cm will be suitable. All patients will underwent mammography, MR of breast, core biopsy of breast tumor, implantation of radiopaque marker into tumor, axillary ultrasound and fine needle biopsy of suspect nodes, CT scan of thorax and abdomen and bone scintigraphy. On core biopsy specimen histologic type, grade, estrogen and progesterone receptors, HER 2 status and MIB-1 will be determined. Additionally, TIL density will be determined on stromal part of tumor on H&E slides in accordance with International TIL Working Group. TIL density will be defined as the percentage of lymphocytes in tumor stroma: as a continuous variable and as two categories: low (0-59%) or high (60-100%). Immunohistochemical detection of CD 20, CD3, CD8, PD-L1, FOXP3 and PGM1 will be performed and each subpopulation of immune cells defined as percentage of all immune cells in tumor stroma. Patients with metastatic tumours and luminal A-like characteristics will be excluded. All other patients will undergo NAST with anthracyclines and taxanes and anti-HER2 therapy if indicated, followed by surgical treatment. The breast and axilla specimen will undergo pathologic examination. pCR will be defined as absence of invasive and carcinoma in situ in breast and axillary nodes. The primary objective will be correlation of CD20, CD3, CD8, PD-L1, FOXP3 and PGM1 with TIL density. The secondary objective will be correlation of subsets of immune cells in tumor stroma with pCR.

Clinical trial identification

EudraCT: 2018-000 547-11.

Legal entity responsible for the study

Institute of Oncology Ljubljana.

Funding

Slovenian Research Agency P3-0321.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

Breast cancer, locally advanced (ID 6627)

Lecture Time
12:00 - 12:00
Speakers
  • Sung-Bae Kim (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00
Poster Display session 2 Poster Display session

292P - BRCA1/2 testing in HER2- advanced breast cancer (ABC): Results from the European component of a multi-country real-world study (ID 4734)

Presentation Number
292P
Lecture Time
12:00 - 12:00
Speakers
  • Michael Patrick Lux (Paderborn, Germany)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Mutations in breast cancer susceptibility gene 1 or 2 (BRCA1/2) are risk factors for developing cancer, especially for breast cancer (BC) and ovarian cancer (OC). Recently, European BC guidelines have expanded the eligibility criteria for BRCA1/2 testing. This study assessed BRCA1/2 testing rates in HER2- adult women with ABC in Germany, France, Italy, Spain and UK (EU5).

Methods

Patient (pt) demographics/clinical characteristics were collected from oncologists in EU5 via Adelphi Advanced Breast Cancer Disease Specific Program. Data collected from 2 years (2015 and 2017) were merged across common variables. Differences in pt demographics/characteristics among BRCA1/2 tested/untested pts were analyzed via t-tests and z-tests. BRCA1/2 testing was analyzed via z-tests. Analyses of BRCA1/2 testing rates were stratified by hormone receptor status [hormone receptor positive (HR+)/HER2- or triple negative breast cancer (TNBC)] and HR status by family history (FHx) of BC or OC.

Results

4,876 records were provided by 742 oncologists. The mean age was 63.6 yrs; 75% HR+/HER2-, 23% TNBC, 2% unknown HR status. Compared to BRCA1/2 untested pts, BRCA1/2 tested pts were younger [57.7 vs 65.2 yrs (p<.001)]and had TNBC [35% vs 20% (p<.001)]. Across all EU5 countries, the mean BRCA1/2 testing rate was 21%; France 20%, Germany 30%, Italy 24%, Spain 20%, UK 14%. Lower BRCA1/2 testing was seen among HR+/HER2- vs TNBC pts [18% vs 33% (p<.001)]. Among HR+/HER2- and TNBC pts, higher BRCA1/2 testing rates were observed among women with a known FHx of BC or OC. (Table). Table. BRCA1/2 Testing by HR Status and known FHx of BC or OC.

HR+/HER2- with FHx (n = 321)HR+/HER2- without FHx (n = 2,953)TNBC with FHx (n = 178)TNBC without FHx (n = 789)
Pts tested, N (%)116 (36)476 (16)99 (56)234 (30)
P value<.001<.001

Conclusions

In this analysis of adult women with ABC, both HR+/HER2- and TNBC pts with a known FHx of BC or OC (vs no known FHx) were more likely to receive BRCA1/2 testing but testing rates are still low especially among HR+/HER2- pts. With the broadening of BRCA1/2 testing eligibility criteria in BC guidelines, opportunities exist to increase BRCA1/2 testing in EU5.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

M.P. Lux: Honoraria (self), Advisory / Consultancy: Pfizer Inc.; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: medac; Honoraria (self), Advisory / Consultancy: Grünethal; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Eisai. A. Niyazov: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

293P - In vitro and in vivo rescue of resistance to BET inhibitors by targeting PLK1 in triple negative breast cancer (ID 1686)

Presentation Number
293P
Lecture Time
12:00 - 12:00
Speakers
  • Cristina Nieto-jiménez (Albacete, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Novel therapeutic strategies are needed for the treatment of triple negative breast cancer (TNBC). Inhibition of bromo and extraterminal domains (BET) has shown an anti-proliferative effect in TNBC as well as a synergistic interaction with polo-like kinase (PLK) inhibitors. As for many other therapeutic interventions, resistance to BET inhibitors is expected to occur at a given treatment point.

Methods

We generated two resistant models to the BET inhibitor JQ1, MDA-MB 231R and HS578TR. Western-blot, flow cytometry analysis, genomic and pharmacologic inhibition were executed to evaluate the anti-proliferative activity and biochemical effect. Nude mice were used to explore the in vivo pharmacological efficacy.

Results

We report the generation of two resistant models to the BET inhibitor JQ1. In both models, resistant cells were particularly sensitive to PLK1 inhibition, and reduced cell proliferation in 2D and 3D cell cultures. Although PLK1 levels were similar in sensitive and resistant cell lines, pharmacological inhibition of BRD4 using JQ1 reduced PLK1 to a less extent in the resistant model, effect not observed with BRD4 gene downregulation. PLK1 inhibitor volasertib induced G2/M arrest in both cell lines, and this effect was more evident in resistant cells, in addition to an increase in pH3 and pCDK1. Combination of volasertib and JQ1 induced apoptosis that was partially caspase dependent. A slight activation of Erk1/2 and pS6 was observed in the resistant model, but the inhibition of these kinases did not have a different effect on proliferation compared with the sensitive one. Finally, JQ1-resistant cells xenografted in mice displayed resistance to JQ1 that was reversed after administration of the PLK1 inhibitor volasertib.

Conclusions

PLK1 inhibition reverts resistance to BET inhibitors in our in vivo and in vitro models. These findings open avenues for further drug combinations in the clinical setting.

Legal entity responsible for the study

Universidad de Castilla-La Mancha.

Funding

Instituto de Salud Carlos III; ACEPAIN; CRIS CANCER; Diputación Albacete; UCLM.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

294P - Neoadjuvant endocrine therapy in combination with melatonin and metformin in locally advanced breast cancer (ID 5020)

Presentation Number
294P
Lecture Time
12:00 - 12:00
Speakers
  • Tatiana Y. Semiglazova (Saint-Petersburg, Russian Federation)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The antitumor effect of melatonin (MLT) and metformin (MTF) has been shown in vitro/in vivo. According to recent data both MLT and MTF may become a new drug which can be used in combination with standard cancer treatment, however, this hypothesis needs confirmation in clinical trials.

Methods

A total of 54 patients with estrogen receptor-positive locally advanced breast cancer (ER+BC) were included in the study of MLT or MTF efficiency in combination with toremifene (TOR) neoadjuvant hormone therapy (clinicalTrials.gov NCT02506790). The average patients’ age was 68 years. All patients had no history of diabetes mellitus. All patients were randomized for 1:1:1 ratio. The first group (n = 19) received 120 mg of oral TOR daily, the second one (n = 16) received TOR in combination with 3 mg overnight dose of oral MLT, the third group (n = 19) received TOR in combination with oral MTF (850 mg twice a day). For all patient groups the hormone therapy duration was 4 months, then surgery was performed.

Results

An objective response rate for three studied groups was 31.6%, 86.7%. and 47.3% accordingly. Adding MLT to TOR lead to significant increase in response rate compared to TOR monotherapy group (χ2 = 10.32, p=0.001). The decrease in Ki67 expression in TOR group was observed in 42%, TOR+ MLT group in 56%, and TOR+MTF group in 74% of patients. According to multivariate analysis of results the TOR combination with MTF leads to 4.2-fold higher Ki-67 expression decrease probability compared to TOR group (OR 4.23 [95% CI 1.044-17.139], p=0.043). Also this group is the only one to display a significant correlation (Spearman) between Ki67 expression decrease dynamics and abnormal BMI values (p=0.015). No pathomorphological response (pCR) was observed. Adding MLT or MTF to standard hormone therapy did not lead to decrease in the quality of life (EORTC-QLQ-C30), about 50% of TOR+MLT therapy recipients had better sleep quality.

Conclusions

MLT and MTF showed encouraging results in combination with neoadjuvant hormonotherapy. However, these data require confirmation in larger randomized studies.

Legal entity responsible for the study

T. Semiglazova.

Funding

Federal State Budget Institution "National Medical Research Center of Oncology na N.N. Petrov" Ministry of Healthcare of Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

295P - Melatonin and metformin in neoadjuvant chemotherapy in locally advanced breast cancer (ID 5082)

Presentation Number
295P
Lecture Time
12:00 - 12:00
Speakers
  • Tatiana Y. Semiglazova (Saint-Petersburg, Russian Federation)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

According to in vitro/in vivo studies both melatonin (MLT) and metformin (MTF) may exhibit an antitumor effect. Furthermore, in accordance to epidemiological studies MTF reduces the risk of developing breast cancer (BC) among patients with diabetes mellitus; as well as “light at night”can inhibit endogenic MLT synthesis and increase risk of breast cancer. Thus, MLT and MTF need to be investigated in clinical oncology.

Methods

A total of 53 patients with locally advanced BC (ER positive/HER2 negative -68%, ER positive/HER2 positive -25% and ER negative/HER2 negative -7%), were included in the study of MLT or MTF efficiency in combination with anthracyclin and taxan-containing neoadjuvant chemotherapy (NACT) (clinicalTrials.gov NCT02506777). The average patients’ age was 56 years. All patients had no history of diabetes mellitus. All patients were randomized into 3 groups. The first group (n = 20) received NACT, the second one (n = 21) received NACT in combination with 3 mg overnight dose of oral MLT, the third group (n = 12) received NACT in combination with oral MTF (850 mg twice a day). For all patient groups the NACT duration was 6 cycles, then surgery was performed.

Results

An objective response rate for three studied groups was 85%, 85.7% and 75% respectively. According to multivariate analysis of results the NACT combination with MLT and MTF does not lead to increase of pathomorphological response (pCR) rate compared to NACT group (OR 0.482 [95% CI 0,083-2,792], p=0.416; OR 0.602 [95% CI 0,085-4,284], p=0.612). pCR rate was in 25%, 14,2% и 16,6% accordingly. The quality of life was assessed by EORTC-QLQ-C30. In the group of patients who received NACT+MLT, in contrast to the group of patients who received only NACT, the values on the role functioning (RF), fatigue (FA) and sleep (SL) scales did not decrease during the treatment (p = 0.008, p = 0.004, p = 0.014 respectively).

Conclusions

MLT and MTF did not show influence on pCR and objective response rates, however, MLT used during NACT may improve the quality of life.

Legal entity responsible for the study

T. Semiglazova.

Funding

Federal State Budget Institution "National Medical Research Center of Oncology na N.N. Petrov" Ministry of Healthcare of Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

296P - Patient-tailored tamoxifen dosing based on an increased quantitative understanding of its complex pharmacokinetics: A novel integrative modelling approach (ID 2642)

Presentation Number
296P
Lecture Time
12:00 - 12:00
Speakers
  • Anna Mueller-schoell (Berlin, Germany)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

About 20% of breast cancer (BC) patients do not attain tamoxifen’s (TAM) active metabolite endoxifen (ENDX) target concentrations when receiving 20 mg TAM once daily (q.d.). Thus, individualised dosing of up to 120 mg TAM q.d. for ENDX target attainment (TA) has been proposed. Combining concentrations and antiestrogenic activities of ENDX and its 3 precursors, the antiestrogenic activity score (AAS) has been developed as alternative TA metric. We aimed to integrate experimental and clinical data from diverse sources in an innovative modelling approach to identify patient groups at risk of treatment failure and to assess whether ENDX- or AAS-guided dosing would be more favourable for TA applying in silico simulation.

Methods

In vitro data from enzyme kinetic experiments, pharmacokinetic (PK) parameters from previous clinical studies and in vivo data from three clinical trials were synthesised into a minimal nonlinear mixed-effects physiologically-based pharmacokinetic (NLME-PBPK) model. Using simulation, lowest doses needed for TA, applying either the ENDX (≥5.97 ng/mL) or the AAS (≥1798) threshold, were investigated in a representative virtual BC population with various CYP2D6 activity scores (AS) and age.

Results

The developed NLME-PBPK model captured individual TAM and 3 metabolite concentration profiles from 406 BC patients well. Bioactivation to ENDX was 4.5-fold higher in CYP2D6 normal (NM) than in poor metabolisers (PM). Patients with low CYP2D6 activity and young age showed highest risks for ENDX non-TA. Among all patients, 76% received the same dose irrespective of the TA metric used. For the remaining 23% with different dose selections, applying the AAS instead of the ENDX target, TA increased in NM and intermediate metabolisers (IM) (+21.7% and +6.9%, respectively), while TA decreased in PM (-11.7%).

Conclusions

Our modelling approach combined pharmacogenetic factors, physiological changes and variability on PK parameters in a quantitative manner and allowed to translate PK information on TAM and its three major metabolites into individualised dosing. While ENDX-guided dosing was preferable for PM in our simulation, AAS-guided dosing was superior for NM and IM.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Klopp-Schulze: Full / Part-time employment: Merck Healthcare KGaA. S.L. Koolen: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Roche; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Cristal Therapeutics; Travel / Accommodation / Expenses: Ipsen. R.H.J. Mathijssen: Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Servier. C. Kloft: Research grant / Funding (institution), Grants received outside the submitted work: DDMoRe; Research grant / Funding (institution), Grants received outside the submitted work: Industry consortium (AbbVie Deutschland GmbH & Co. KG, Boehringer Ingelheim Pharma GmbH & Co. KG, Gruenenthal GmbH, F. Hoffmann-La Roche Ltd., Merck KGaA and SANOFI); Research grant / Funding (institution), Grants received outside the submitted work: Federal Ministry of Education and Research; Research grant / Funding (institution), Grants received outside the submitted work: Diurnal Ltd. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

297P - Lack of benefit of neoadjuvant pertuzumab in high risk HER2 positive breast cancer: A retrospective case-control study of 355 cases with biomarker analysis (ID 2461)

Presentation Number
297P
Lecture Time
12:00 - 12:00
Speakers
  • Manuela Tiako Meyo (Paris, France)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The NEOSPHERE trial suggested that pertuzumab (P) added to a combination of docetaxel and trastuzumab (T) as a neoadjuvant therapy in HER2 positive breast cancer (HER2+ BC) patients (pts) significantly enhances pathological complete response (pCR) rates. Here, we report our institution experience, focusing on stage III tumors.

Methods

We reviewed clinical and pathological response (residual cancer burden, RCB) in 355 HER2+ BC treated between 2010 and 2017 with neoadjuvant chemotherapy combined with T (n = 291) or TP (n = 64). Results were adjusted according to clinical stage, hormone receptors (HR) status, and chemotherapy regimen. In a subset of 157 pts matched on clinical TNM stage and HR expression (T, n = 98; TP, n = 59), a baseline pathological biomarker analysis was performed to assess TILs, PTEN, FOXP3 and PD-L1 expression.

Results

Among 355 patients, tumor clinical stages were T3 -T4 for 40% vs. 72% of T and TP pts (p < 0.0001). HR were expressed in 40% of T group and 22% of TP group (p = 0.002). Most tumors were grade 3 (63% in both groups). Almost all pts received taxanes, and 81% (T) vs. 69% (TP) received anthracyclines (p = 0.03). Breast conserving surgery (BCS) was performed in 52% (T) and 34% (TP) of pts (p = 0.008). pCR (RCB=0) was observed in 43% and 51% of T and TP groups, respectively (p = 0.25). For stage III pts, pCR was achieved in 48% (T) and 53% (TP) of pts (p = 0.25). Multivariate analyses did not show any independent factor associated with pCR. Features of the biomarker subset were similar among both groups: stage III=81%; HR negative=70%; grade 3=63%; anthracyclines 79% (T) and 68% (p = 0.09); BCS=31%. RCB=0 was seen in 50% (T) and 53% (TP) of pts (p = 0.93). Immune cells infiltration (CD8+, PD-L1+ and FOXP3+ lymphocytes) and tumor PD-L1 expression rates were higher in TP group (p < 0.0001). None of the pathological biomarkers correlated with pathological response.

Conclusions

This retrospective study did not suggest any benefit of neoadjuvant TP dual HER2 blockade regarding pathological response for stage III HER2+ BC. Baseline pathological expressions of PTEN, FOXP3, TILs, PD-L1 did not correlate with pathological response.

Legal entity responsible for the study

Institut Curie.

Funding

Institut Curie.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

298P - Targeting CDCA3 to improve chemotherapy response in triple negative breast cancer patients (ID 4776)

Presentation Number
298P
Lecture Time
12:00 - 12:00
Speakers
  • Kenneth J. O'Byrne (Woolloongabba, QLD, Australia)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer is the second most diagnosed cancer globally accounting for over 2 million new worldwide cases of the disease in 2017. Chemotherapy (including cyclophosphamide and anthracyclines) is the mainstay for triple-negative breast cancer (TNBC) treatment. Despite high rates of responses to neoadjuvant chemotherapy, TNBC patients experience high rates of distant recurrence and less than 30% of patients with metastatic disease treated with chemotherapy will survive 5 years. These poor cancer patient outcomes highlight the need for novel companion diagnostics and therapies to identify the patients who will derive benefit and improve the response to therapy. Herein, we have identified ‘cell division cycle associated protein 3’ (CDCA3) as a novel protein that may prove useful to enhance chemotherapy response in TNBC.

Methods

Bioinformatics, Western blot, immunohistochemistry, siRNA depletion of CDCA3, CRISPR-Cas9 knockout, dose response, cell viability.

Results

CDCA3 transcripts are elevated across increasing grades of breast cancer, TNBC versus non-TNBC and in basal-like (BLIA and BLIS) versus luminal-AR and mesenchymal TNBC subtypes (METABRIC datasets). Elevated CDCA3 levels were strongly prognostic for patient outcome in high grade breast cancer and TNBC. Tissue microarray (TMA) immunohistochemistry analysis of over 300 breast cancers indicated heterogeneous CDCA3 staining is strongly prognostic in Ki67+ and TNBC cases of disease. CDCA3 staining correlated with markers of poor prognosis (nuclear grade, mitotic score, nuclear pleomorphism) and was associated with a poor prognosis. In vitro, we identified that, consistent with clinical data, CDCA3 levels were elevated in TNBC versus non-TNBC cell lines. In 10 TNBC cell lines, endogenous CDCA3 expression correlated with sensitivity to both cisplatin and doxorubicin, with CDCA3high levels having higher IC50 values and thereby being associated with a poor prognosis. Consistently, depleting these cells of CDCA3 markedly enhanced sensitivity to both cisplatin and doxorubicin.

Conclusions

Our data highlight CDCA3 as a novel prognostic factor in TNBC that modulates sensitivity to chemotherapy. These findings point to the therapeutic potential of targeting CDCA3 in TNBC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

299P - Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer (ID 1674)

Presentation Number
299P
Lecture Time
12:00 - 12:00
Speakers
  • María Del Mar Noblejas Lopez (Albacete, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Triple negative breast cancer (TNBC) is an incurable disease, therefore novel therapies are needed. Bromo and extraterminal domain inhibitors (BETi) are currently in clinical development with promising activity in TNBC. However, resistance to these agents will limit their efficacy. Proteolysis targeting chimeric (PROTAC) are novel compounds that by binding to a ubiquitin ligase promotes protein degradation.

Methods

In our study we explore the antitumoral activity of two BET-PROTACs, MZ1 and ARV-825 in TNBC and ovarian cancer. We used MDAMB-231, BT549 and MDAMB-231 JQ1 resistant TNBC cells lines; and OVCAR3 and SKOV3 ovarian cancer cells lines. We evaluated the antiproliferation effect using MTT assay, colony-forming assay and three-dimensional cultures in Matrigel. To explore the molecular mechanism of drugs we used flow cytometry (cell cycle and cell death). The analysis of protein expression was determined by western blot. In vivo studies included BALB/c nu/nu mice that were injected with MDAMB-231 JQ1 resistant cells and later treated with BETi JQ1 and BET-PROTAC MZ1.

Results

Both PROTACs efficiently and maintained deleted the levels of BRD4 in MDA-MB-231 and in the resistant JQ1 cell line MDA-MB-231R. MZ1 and ARV-825 showed a profound antiproliferative effect in MDA-MD-231 sensitive and resistant cells using 2D and 3D cultures, and had a similar activity in other triple negative (BT549) and ovarian cancer (SKOV3, OVCAR) cell lines. MZ1 slightly arrested cells at G2/M in sensitive and resistant JQ1 MDA-MB-231 cells. In addition, a profound effect on apoptosis was observed, that was more evident in the sensitive cell line, effect that was caspase dependent. Given the potent antiproliferative activity of MZ1 no synergistic activity was observed when combined with docetaxel, cisplation or olaparib. Finally, administration of MZ1 was able to recue tumor growth in nude mice of MDA-MB-231 JQ1 resistant cells, by reducing the expression of BRD4.

Conclusions

We describe the profound activity of BET-PROTACs in TNBC cell lines and in an in vivo BETi resistant model. This data provides options for further clinical development of these agents in TNBC.

Legal entity responsible for the study

The authors.

Funding

Instituto de Salud Carlos III (PI16/01121), ACEPAIN; Diputación de Albacete, CIBERONC, CRIS Cancer Foundation, implementation research program of the UCLM System of Science, Technology and Innovation-Secti (co-funded by the European Commission/FSE funds) and scientific foundation of the AECC.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

300P - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumour infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion (ID 5629)

Presentation Number
300P
Lecture Time
12:00 - 12:00
Speakers
  • Luca Campedel (Paris, CEDEX 13, France)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Inflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis.

Methods

Between January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80 mg/m2) qw or 4 injections of docetaxel (100 mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TIL was defined as the difference between post chemotherapy and pre chemotherapy TIL.

Results

Thirty TNIBC patients were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 45 months (8 – 103). 9/30 patients (30%) achieved pCR. Median disease free survival was not reached. Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). On univariate analysis, LVI after chemotherapy (HR = 2.1 [95% CI, 1.1–3.6], p = 0.02), TIL on mastectomy (HR = 1.8 [95% CI, 1.1–3.1], p = 0.03), delta TIL (HR = 2.2 [95% CI, 1.4–3.5], p = 0,001) were associated with DFS but no pCR (p = 0,051). On multivariate analysis, only delta TIL remainedstatistically significant (HR = 1.9 [95% CI, 1.1–3.4], p = 0.03).

Conclusions

We showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Delta TIL is a strong prognostic factor associated with DFS. We show that a positive Delta TILis, among others, a strong and independent predictor of DFS: in TNIBC contrary to the results obtained in TN non inflammatory breast cancers, an increase in TIL after chemotherapy is associated with a decrease in DFS.The exact impact of LVI must be further investigated.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

301P - A novel PET parameter for cancer stem cell metabolism: Early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer (ID 5792)

Presentation Number
301P
Lecture Time
12:00 - 12:00
Speakers
  • Chanwoo Kim (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Early predicting the pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with locally advanced breast cancer (LABC) is closely associated with clinical outcomes. However, conventional metabolic parameters using baseline 18F-FDG PET/CT have failed to accurately predict the pCR. Breast cancer stem cells (CSCs) are known for their established role in chemoresistance. We designed a new PET parameter for CSC metabolism (MTVcsc) from pretreatment 18F-FDG PET/CT by using distinctive glucose metabolism between CSCs and differentiated cancer cells, and aimed to evaluate the prognostic value of the MTVcsc.

Methods

A total of 71 patients with LABC who underwent initial 18F-FDG PET/CT before NAC were included in this study. The SUV values of single voxels within the primary tumor were clustered by performing k-means clustering using R version 3.5.3 and MTVcsc was derived by calculating the volume of the most glycolytic cluster. The predictive values of the MTVcsc, as well as clinicopathologic and conventional metabolic parameters (SUVmax, MTV, TLG) for pCR, were analyzed by multivariable logistic regression.

Results

Seventeen patients were excluded from the final analysis due to small tumor size (< 64 voxels). The lower MTVcsc and non-luminal subtypes were significantly associated with achieving pCR following NAC (Table). The MTVcsc outperformed the conventional PET parameters in predicting pCR. Table Univariable and multivariable logistic regression model of clinicopathologic and metabolic parameters for predicting pathologic complete response.

ParametersUnivariable analysis
Multivariable analysis
OR95% CIP valueOR95% CIP value
Ki-67
Low, < 20% High, ≥ 20%1.00
5.571.06-29.270.043
Molecular subtype
Luminal A and B HER2 positive Triple negative1.001.00
11.462.07-63.360.00513.71.75-107.360.013
6.551.05-40.670.04417.421.41-215.040.026
Metabolic parameters
SUVmax Metabolic tumor volume (MTV) Total lesion glycolysis (TLG) MTVcsc0.980.83-1.160.814
0.980.94-1.020.281
0.990.98-1.000.231
0.290.10-0.890.0310.210.05-0.820.025

Conclusions

MTVcsc, a novel PET parameter for CSC metabolism, provides predictive value for pCR. By further stratifying LABC patients with a combination of MTVcsc and molecular subtype at initial staging workup, achieving pCR after NAC can be early predicted more accurately.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

302P - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer (ID 3728)

Presentation Number
302P
Lecture Time
12:00 - 12:00
Speakers
  • Besma Graja (Tunis, Tunisia)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The purpose of this study was to evaluate the prognostic value of nodal ratio compared to the absolute number of positive lymph nodes in patients with ≥4 positives nodes early-stage breast cancer.

Methods

Between 2010-2015, we identified 111 patients with early-stage pN2-N3 breast cancer. All patients were treated with curative intent and had at least 8 resected lymph nodes. We calculated nodal ratio (NR=positive over excised lymph nodes) for each patient. Several prognostic factors were evaluated. The Cox proportional hazard model was used to evaluate the prognostic significance for relapse-free survival and overall survival.

Results

Median age was 50 years old. Lymph node involvement was pN2 in 61.3% of cases and pN3 in 38.7% of cases. Median tumor size was 46 mm. Hormonal receptors were positive in 73.9% of cases. Her2 Neu was overexpressed in 32.4% of cases. Relapse rate was 34.2% (locoregional 36.2%, metastatic in 63.8%). After a median follow-up of 44 months, we did not observe any difference in terms of relapse rate (30% vs 40%, p = 0.19), time to relapse (25 months, p = 0.94), relapse-free survival and overall survival according to absolute number of involved lymph nodes (pN2 vs pN3 groups). NR ≥ 60% was significantly correlated with relapse rate (24% vs 53%, p = 0.02). There was no impact of NR on time to relapse (24 vs 26 months p = 0.81). In univariate analysis we observed a significant difference in 5-year relapse-free survival between patients with NR < 60% vs NR ≥ 60% (59% vs 49%, p = 0.04). In multivariate analysis including: grade, hormonal receptors, HER2, Ki67, we observed that NR was as an independent prognostic factor for relapse-free survival. There was no impact on overall survival.

Conclusions

NR ≥ 60% predicted relapse-free survival better than the absolute number of involved lymph nodes in pN2 and pN3 early-stage breast cancer.

Legal entity responsible for the study

Abderrahmen Mami Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

303P - Re-sentinel node biopsy for local recurrence after breast-conserving surgery (ID 3395)

Presentation Number
303P
Lecture Time
12:00 - 12:00
Speakers
  • Yuka Matsubara (Yokohama, Japan)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The usefulness of re-sentinel node biopsy (re-SNB) is unclear in the management of patients with ipsilateral recurrent breast cancer.

Methods

We retrospectively reviewed 52 patients with locally recurrent breast cancer who underwent re-SNB from July 2012 to March 2019. Both radioactive colloid and indocyanine green were used in all cases.

Results

Forty-four patients were after SNB and 8 were after axillary lymph node dissection(ALND). SLNs were successfully visualized by lymphoscintigraphy in 94.2% (49/52) of cases (95.4% post-SNB vs. 87.5% post-ALND, Fisher’s exact test, p = 0.401). Among post-SNB patients with successful mapping, 50% had SLNs only in ipsilateral axilla(I) and 50% had at least one SLN in other regions(contralateral axilla [C] and/or parasternal region [P])with or without SLN in (I), compared to 28.6% and 71.4% in post-ALND cases respectively(p = 0.424). Among post-SNB cases with prior breast irradiation (n = 37), 44.4% had SLN only in (I) and 55.6% had at least one SLN in other regions, compared to 83.3% and 16.7% in cases without prior irradiation (n = 7) (p = 0.184), respectively. While these differences were not significant, a lower rate of visualization and higher frequency of aberrant lymphatic flow in post-ALND than those in post-SNB was noted, and prior irradiation might affect lymphatic flow. We tried re-SNB for 47 cases and SLNs were successfully removed in 45 (95.7%) patients (92.8% in post-SNB, 100% in post-ALND). Re-SNB for (I) was performed for all cases with hot spots in (I) and one case without hot spot. Re-SNB for (C) or (P) were decided based on physician’s judgment. The SLN identification rates by site were 92.1% (35/38) for (I), 90.0% (9/10) for (C), and 100% (3/3) for (P). Sentinel node metastasis was found in three cases, all of which were in (I). ALND was performed in one case with macrometastasis but was omitted in two cases with micrometastases. The median follow-up duration after re-SNB was 22 months and no recurrence was observed.

Conclusions

Sentinel node identification was possible with high detection rates among patients with recurrent breast cancer after prior breast-conserving and axillary surgery.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Yamanaka: Honoraria (self): Chugai; Honoraria (self): Eisai; Honoraria (self): Novartis Pharma; Honoraria (self): Taiho; Honoraria (self): Phizer Japan. T. Yamashita: Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self): Eisai; Honoraria (self): Novartis Pharma; Honoraria (self): Taiho; Honoraria (self), Research grant / Funding (institution): Nippon Kayaku; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Kyowa kirin; Honoraria (self): Phizer Japan; Honoraria (self): Takeda. N. Suganuma: Honoraria (self): Eisai; Honoraria (self): Novartis Pharma; Honoraria (self): Taiho; Honoraria (self): Kyowa kirin; Honoraria (self): Phizer Japan. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

304P - Assessment of prognostic and therapeutic factors in men with breast cancer (ID 4302)

Presentation Number
304P
Lecture Time
12:00 - 12:00
Speakers
  • DANIEL HERRERO RIVERA (Sevilla, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer in men is rare, assuming less than 1% of diagnosed breast cancer, requiring extrapolation of results from studies in women. Our objective is to evaluate prognostic and therapeutic factors paying special attention to the effect of hormonal treatment on the evolution of the disease.

Methods

Observational, retrospective, single-center study of 53 men with breast cancer treated between January 1997 and December 2018. The median follow-up was 66 months (range, 3-282 months). 48 patients had ECOG 0-1 (90.6%), 48 were hormone-receptor-positive (90.5%) and 4 HER2-positive (7.5%). 30 patients had lymph node involvement at diagnosis (56.6%). A total of 45 patients (84.9%) were treated with endocrine therapy (ET) of which 36 received it in adjuvant (67.9%) and 13 in metastatic phase (24.5%). 26 (49.1%) were treated with chemotherapy and 3 with cyclin-dependent kinase inhibitors (5.6%). The association analysis was performed using the Chi-square test and survival analysis with the Log-Rank test in SPSS v25.

Results

Our cohort had a median age of 68 years (range, 40-88 years). 84% had local or locally advanced stage. The infiltrative histologies were 88.7%. The BRCA gen test was carried out in 43.4%, which was positive in 26.1% of the analyzed patients, with BRCA2 being associated with lower mortality (p = 0.004). The statistic analysis showed greater 5-year overall survival (OS) and cancer-specific survival for ECOG 0-1 (p = 0.010, p = 0.048), absence of vascular invasion (p = 0.033, p = 0.025), Ki67 <14% (p = 0.041; p = 0.029) and absence of metastasis at diagnosis (p < 0.0001, p < 0.0001). In relation to ET, they had higher 5-year disease-free survival (OR 0.35, p = 0.001), and lower risk of distant relapse (OR 0.56, p = 0.034) those who received adjuvant ET ≥ 5 years, as well as lower risk of relapse at distance if they received LHRH agonists (OR 0.37, p = 0.022).

Conclusions

The existence of prognostic factors already described in breast cancer in women also seem to be associated with men. The BRCA2 mutation could have a significant role as a predictive marker in males in the near future. ET helps reducing the risk of relapse, particularly at distance.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F.J. Salvador Bofil: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis M. Ruiz Borrego: Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

Breast cancer, metastatic (ID 6628)

Lecture Time
12:00 - 12:00
Speakers
  • Sung-Bae Kim (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00
Poster Display session 2 Poster Display session

312P - Genomic profiling of Chinese breast cancer patients (ID 4263)

Presentation Number
312P
Lecture Time
12:00 - 12:00
Speakers
  • Zhonghua Tao (Shanghai, China)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The complexity of breast cancer (BC) at the clinical, morphological and molecular level has been well demonstrated. Molecular profiling, which reveals the intrinsic biology among subtypes, has significantly advanced the management of this disease. However, previous studies have provided very limited molecular data on Chinese BC patients.

Methods

We performed capture-based targeted sequencing on plasma samples using a panel consisting of 102 BC related genes, spanning 249 kb of human genome, to interrogate the genomic landscape of 236 female Chinese BC patients and compared our results to the TCGA data set. Only genes covered by the panel and occurring in more than 10% patients from at least one subgroup were compared and contrasted between the two cohorts. The Chinese and the TCGA cohort had a median age of 48 and 58, respectively.

Results

Our cohort consisted of 55% triple negative breast cancer (TNBC), 10% luminal A, 27% luminal B and 8% HER2 positive BC. 53% of patients were post-menopausal. 190 patients had mutations found from this panel, resulting in a positive detection rate of 81%. Of the 46 patients with no mutation detected from this panel, 24 had TNBC. Collectively, we identified 921 mutations spanning 89 genes. First, we compared and contrasted mutation spectrum among the 4 subtypes. TP53mutations were more commonly seen in TNBC patients (p < 0.01), whereas FGF3, FGF4, FGF19and CCND1amplification were more likely to occur in patients with Lumina A or Luminal B BC (p = 0.002). Next, we compared the mutation spectrum of our cohort to TCGA dataset, and for luminal B breast cancer and TNBC, Chinese patients had significantly more PI3KCA mutation found. Furthermore, Chinese luminal A (p < 0.01) and luminal B (p < 0.01) patients had significantly higher TP53mutation frequency and Chinese HER2 positive BC patients (p < 0.01) had significantly lower TP53mutation frequency than TCGA dataset. In addition, we also identified 10 pathogenic or likely pathogenic BRCA1/2 mutations from this cohort, resulting in a prevalence rate of 4.2%.

Conclusions

We identified distinctive genomic patterns associated with Chinese breast cancer patients compared to TCGA data, suggesting the importance of mutation-based stratification according to ethnic status.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

313P - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer (ID 2406)

Presentation Number
313P
Lecture Time
12:00 - 12:00
Speakers
  • Naomi Walsh (Dublin, Ireland)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The introduction of anti-HER2 therapies such as trastuzumab for HER2+ metastatic breast cancer (MBC) has led to significant improvements to disease progression. We, and others have reported cases of long-term durable complete response to trastuzumab in HER2+ MBC. However, to-date only clinical and molecular analysis of this “exceptional” cohort exists. We hypothesise that genomic copy number alteration (CNA) burden can act as a prognostic measure of predicting response to trastuzumab in long-term never relapse exceptional responders (ExRs) from rapid non-responders (NR).

Methods

We performed whole exome sequencing (WES) on n = 6 never relapse ExRs (med RFS < 149 mo) and n = 5 corresponding NRs (median RFS < 14 mo). Both tumour and adjacent normal tissue (where available) was sequenced by BGI using the NGS illumina HiSeq PR100 (2 x 100 bp) at a mean depth of 56 x. Reads were aligned to the hg19 reference genome using BWA software. Two-sample t-test with unequal variances was used to evaluate total genome CNA burden. Median CNA burden was used to stratify patients into high and low CNA burden groups, binary CNA stratification groups were further assessed using Kaplan-Meier survival estimation.

Results

We analysed the DNA chromosome disruption (fraction of the genome amplified/deleted) and present CNA burden. We observed the overall fraction of genome CNA burden was more destructed (P = 0.07); while more significantly pronounced in the amplification of the whole genome (P = 0.03) in NR compared to ExRs. We further delineated the distribution of CNA burden in all genomes and identified chromosome 8 as significantly disrupted in NRs (P = 0.02). Kaplan Meier survival analysis revealed that low total CNA burden at Chr8 and Chr17 conferred a statistically significant benefit in overall survival (P = 0.009 and P = 0.016, log rank).

Conclusions

CNA burden in HER2+ MBC exceptional responders may represent a novel prognostic predictor to trastuzumab response. Our investigation of genome-wide CNA burden offers the potential to gain insight into the underlying genetic landscape of long-term, never relapse exceptional response to trastuzumab.

Legal entity responsible for the study

The authors.

Funding

Cancer Clinical Research Trust.

Disclosure

G. Gullo: Honoraria (self): Genomic Health; Travel / Accommodation / Expenses: Roche. J. Crown: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Shareholder / Stockholder / Stock options: OncoMark; Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (institution): Puma Technology; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self): Vertex; Honoraria (self): Genomic Health; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): MSD Oncology. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

314P - Next-generation DNA sequencing (NGS) results for tumours from phase II ABRAZO study of talazoparib after platinum or cytotoxic non-platinum regimens in patients (pts) with advanced breast cancer (ABC) and germline BRCA1/2 (gBRCA) mutations (ID 2575)

Presentation Number
314P
Lecture Time
12:00 - 12:00
Speakers
  • Nicholas C. Turner (London, United Kingdom)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Loss-of-function mutations in genes encoding components of the homologous recombination (HR) machinery are associated with tumor sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. In ABRAZO, the PARP inhibitor talazoparib demonstrated encouraging efficacy in gBRCA-mutated ABC, both in pts whose cancer responded to prior platinum therapy (cohort 1) and in pts who had received ≥3 prior nonplatinum chemotherapy regimens for ABC (cohort 2).

Methods

Baseline tumor tissue (primary or metastatic sites) from enrolled pts was sequenced using the FoundationOne CDx NGS panel. 60/84 pts (71%) in the intent-to-treat population had available tumor tissue, which could be sequenced. Mutations summarized below were known or likely pathogenic single-nucleotide variants, insertions, deletions, or rearrangements. Additional exploratory computational analyses pertinent to HR deficiency were performed, including genomic loss of heterozygosity (gLOH) and somatic-germline-zygosity assessments.

Results

Tumor mutations in BRCA1 and BRCA2 were detected in 29 (48%) and 28 (47%) of 60 evaluable pts (no pts exhibited mutations in both BRCA1 and BRCA2). These mutations were most commonly single-nucleotide variants (BRCA1: 12 [20%] and BRCA2: 10 [17%]) or deletions (BRCA1: 11 [18%] and BRCA2: 12 [20%]). Mutations in other genes implicated in HR were comparatively rare, with mutations in CHEK2 (2 pts), ARID1A, ATR, BARD1, BRD4, BRIP1, FANCC, and STAG2 (each in single pts) detected. In addition to BRCA1/2, genes where mutations were detected in ≥ 10% of evaluable pts included TP53 (45%) and PIK3CA (12%). TP53 mutations were more commonly observed in BRCA1-mutated than in BRCA2-mutated tumors (22/29 [76%] compared with 4/28 [14%]). Associations of genetic/genomic events with progression-free survival will be presented.

Conclusions

NGS of tumors from the ABRAZO study of talazoparib in patients with gBRCA-mutated ABC revealed a complex mutational landscape. Exploratory correlative analyses are ongoing and will be reported.

Clinical trial identification

NCT02034916.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

N.C. Turner: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Inc.; Advisory / Consultancy, Research grant / Funding (institution): BioMarin. A..D. Laird: Full / Part-time employment: Pfizer Inc. M.L. Telli: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Advisory / Consultancy, Research grant / Funding (institution): Vertex; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoSec; Research grant / Funding (institution): Sanofi. H.S. Rugo: Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma. A. Mailliez: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Advisory / Consultancy: Vertex; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoSec; Research grant / Funding (institution): Pfizer Inc. J. Ettl: Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (institution), Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Eisai; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self): TEVA; Honoraria (self): AstraZeneca. J. Balmaña: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZenca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: BMS; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharMar. P.A. Fasching: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Puma; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Teva; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (institution), Speaker Bureau / Expert testimony: Myelo; Research grant / Funding (institution): BioNTech. S.A. Hurvitz: Research grant / Funding (institution): Ambryx; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BI Pharma; Research grant / Funding (institution): Biomarin; Research grant / Funding (institution): Cascadian; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Dignitana; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Roche. L.A. Albacker: Full / Part-time employment: Foundation Medicine Inc. G.M. Frampton: Full / Part-time employment: Foundation Medicine Inc. J. Chelliserry: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. P. Bycott: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. U. Conte: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. A.M. Wardley: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche. M.E. Robson: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: McKesson; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): BioMarin; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Myriad Genetics; Research grant / Funding (institution): Tesaro. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

315P - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors (ID 4499)

Presentation Number
315P
Lecture Time
12:00 - 12:00
Speakers
  • Evgeny Imyanitov (Saint-Petersburg, Russian Federation)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Several lines of evidence suggest the involvement of CCND1 and FGFR1 genes in determining breast cancer (BC) resistance to endocrine therapy, however these assumptions still require a validation in clinical data sets.

Methods

This study included 138 tumors from patients with metastatic BC who received first-line endocrine therapy with aromatase inhibitors (AI, n = 69), tamoxifen (n = 65), goserelin (n = 2) or a combination of goserelin and tamoxifen (n = 2). DNA extracted from formalin-fixed paraffin-embedded archival specimens was tested for CCND1 and FGFR1 amplification by digital droplet PCR.

Results

CCND1 and FGFR1 status was successfully determined in 134 tumors. CCND1 and FGFR1 amplification was detected in 24 (18%) and 28 (21%) informative cases, respectively; 9 carcinomas had concurrent alterations of two genes. Amplifications were more common in less differentiated tumors (G1: 1/18 (6%) vs. G2-3: 34/86 (40%); p = 0.005, Fisher’s exact test). Median disease-free survival in patients receiving AI with CCND1 amplification was shorter than in cases with the normal gene status (12.3 vs. 14.9 months; p = 0.014, log rank test). Objective response to aromatase inhibitors was observed in 2/13 (15%) BC with FGFR1 amplification compared to 22/46 (48%) tumors with the normal FGFR1 gene copy number (p = 0.054). Noteworthy, among patients receiving AI, CCND1 and/or FGFR1 amplification occurred in 5 out of 7 (71%) women with progressive disease compared to only 4 in 23 (17%) patients with objective response to therapy (p = 0.01). Meanwhile, none of 5 tumors showing resistance to tamoxifen harbored CCND1 or FGFR1 amplification.

Conclusions

The presence of CCND1 and/or FGFR1 amplification is associated with worse results of AI therapy in breast cancer patients.

Legal entity responsible for the study

The authors.

Funding

Russian Foundation for Basic Research (grant 17-04-01281).

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

316P - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe experience (ID 4110)

Presentation Number
316P
Lecture Time
12:00 - 12:00
Speakers
  • Sercan Aksoy (Ankara, Turkey)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Impaired DNA damage response (DDR) mechanisms and subsequent genomic instability is associated with carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. As a result, BRCA1/2 testing is recommended for a group individuals with breast/ovarian cancer.

Methods

In this study, we retrospectively invesitigated clinicopathologic features of 303 breast cancer patients tested for BRCA 1/2 mutation in an oncology institute. NCCN recommendations are used to select patients to be tested for BRCA mutations.

Results

A total of 303 patients were analysed for BRCA 1/2 mutations. Median age of the patients at diagnoses were 40 (21-65). Family history for BRCA related cancers were detected in 120 patients (39.6%). BRCA 1/2 mutations have been shown in 98 of 303 patients (32.3%). Of 98 BRCA mutated patients, 43 had pathogenic BRCA1 mutation, 39 had pathogenic BRCA2 mutation, 11 had variant of uncertain significance (VUS) BRCA2 mutation, 3 had VUS BRCA1 mutation and 2 had pathogenic BRCA1 and 2 mutations. Molecular subtypes of tumors have been shown in Table.

316P Molecular subtypes of tumors

BRCA StatusHR(+)/ HER2(-), N(%)HR(+)/ HER2(+), N(%)HR(-)/ HER2(+), N (%)Triple(-), N (%)N/A,N(%)
BRCA118 (41.8%)2 (4.6%)022 (51.1%)1 (2.3%)
BRCA225 (64.1%)3 (7.7%)06 (15.3%)5 (12.8%)
BRCA1 VUS2 (66.7%)001 (33.3%)0
BRCA2 VUS11 (100%)0000
BRCA1 + 201 (50%)01 (50%)0
BRCA mut (-)126 (61.4%)25 (12.1%)12 (5.8%)32 (15.6%)10 (4.8%)
TOTAL182 (60%)31 (10.2%)12 (3.9%)62 (20.4%)16 (5.2%)

Twelve of 98 BRCA mutated patients (12.2%) were de novo metastatic while 15 patients (15.3%) faced with metastatic disease during follow-up. In the BRCA mutated group there was significantly high rate of metastatic disease has been detected comparing BRCA non-mutated group (27.5% vs %16.5% respectively, p = 0.026). Metastatic BRCA mutant patients showed worse OS numerically but data is not statistically significant (P = 0.894). Nine patients were diagnosed with contralateral breast cancer, and 3 patients was diagnosed with BRCA-related cancers during follow-up. Prophylactic surgery (contralateral mastectomy and/or oophorectomy) was performed in 32 of 98 patients.

Conclusions

According to this retrospective study, BRCA mutant patients tend to have worse clinical and pathological features comparing age-matched controls.

Legal entity responsible for the study

Sercan Aksoy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

317P - Novel fusion genes identified from matched primary and recurrent breast cancers by RNA-sequencing (ID 5203)

Presentation Number
317P
Lecture Time
12:00 - 12:00
Speakers
  • Soojeong Choi (Seoul, Korea, Republic of)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancers display substantial inter/intra-tumor heterogeneity. While numerous fusion genes have been identified, most are found to be subclonal, passenger alterations. To discover fusion genes which drive tumor progression and metastasis, we performed RNA-sequencing of matched primary and metastatic breast cancer samples.

Methods

RNA-sequencing was performed from sixteen patients matched primary-recurrent tumor tissue and RNA-sequencing data was successfully achieved from sixteen primary tumors and eight recurrent tumors. DeFuse program was used to identify fusion transcripts (FT).

Results

Among the sixteen patients, six were hormone receptor positive, three were HER2 positive and seven were triple negative tumors. Three cases displayed loco-regional recurrence only and other patients had distant metastases. Overall, 516 fusion transcripts were identified. Mean numbers of fusions in primary and recurred tumors were 28 and 14.6 FTs per sample. Numbers of fusions were greater in two cases with BRCA1 pathogenic germline mutations while no significant differences were observed across subtypes. Novel inter-chromosomal fusion transcript, BCL2-ESR1, CSMD1-ESR1 and HPGDS-ESR1 were found in one hormone receptor positive patient’s metastasis and/or primary tumor. All fusions resulted in preservation of the DNA-binding domain and ligand-binding domain (exon4-10) of the ESR1 gene, with high ESR1 FPKM expression value. Fusions of ERBB2-, MALAT1- and CDK6- genes were found. Among the identified FTs, three cases harbored a previously reported recurrent fusion transcript EEF1DP3-FRY.

Conclusions

RNA sequencing revealed numerous fusion transcripts. Among them we found novel fusions including ESR1 fusions which need further validation and functional annotation to confirm their role in tumor progression and metastasis.

Legal entity responsible for the study

The authors.

Funding

Asan Medical Center.

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

318P - Association between PIK3CA mutation status and development of brain metastases in HR+/HER2- metastatic breast cancer (ID 5873)

Presentation Number
318P
Lecture Time
12:00 - 12:00
Speakers
  • Donna M. Fitzgerald (Boston, United States of America)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

CNS metastases is a devastating complication of breast cancer, occurring in approximately 10%–15% of patients with metastatic breast cancer (MBC) and resulting in median survival of less than one year in historic cohorts. Biological factors that govern metastases to the brain, including the role of activating PIK3CA mutations, the most common actionable alterations in HR+/HER2- MBC, are poorly understood.

Methods

In this retrospective cohort study, we determined the cumulative incidence of brain metastasis in PIK3CA mutant and PIK3CA non-mutant HR+/HER2- MBC patients treated at the Massachusetts General Hospital and genotyped during their routine clinical care with a highly sensitive multiplexed assay for real time mutation profiling of clinical samples.

Results

In the overall cohort of 307 patients, 120 patients (39.1%) had PIK3CA mutant disease and 187 patients (60.9%) had PIK3CA non-mutant disease, comparable to previously published results. Median OS from the time of diagnosis of metastatic disease was 3.96 yrs (95% CI 3.40-4.87 yrs) for PIK3CA mutant patients and 4.43 yrs (95% CI 3.82-5.32 yrs) for PIK3CA non-mutant patients, p = 0.6. 22.44% of patients with HR+/HER2- disease developed brain metastases; 30.83% of PIK3CA mutant patients and 17.11% of PIK3CA non-mutant patients developed CNS metastases, p = 0.0049. Median time to the development of CNS disease was 8.61 yrs for PIK3CA mutant subset and not reached (NR) for PIK3CA non-mutant subset, p = 0.0086. Among patients with CNS metastases, median OS for PIK3CA mutant patients was 0.48 yrs (95% CI 0.27-0.74) and for PIK3CA non-mutant it was 1.09 yrs (95% CI 0.39-2.27), p = 0.019).

Conclusions

Brain metastases are common in HR+/HER2- MBC. This incidence of brain metastases is particularly high among patients with HR+/HER2- tumors harboring a PIK3CA mutation, where it approaches the incidence historically seen in HER2+ MBC. Early recognition of symptoms potentially related to brain metastases is important even in HR+/HER2- subtype of breast cancer. High incidence of brain metastases in PIK3CA mutant HR+/HER2- MBC warrants development of blood-brain barrier penetrant agents targeting the PI3K/AKT/mTOR pathway.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S. Isakoff: Advisory / Consultancy, Research grant / Funding (institution): Myriad; Advisory / Consultancy, Research grant / Funding (institution): Puma; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Mylan; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Pharmamar; Advisory / Consultancy, Research grant / Funding (institution): Abbvie; Advisory / Consultancy, Research grant / Funding (institution): OncoPep; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. A. Bardia: Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Radius Health; Advisory / Consultancy, Research grant / Funding (institution): Specturm; Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Innocrin; Research grant / Funding (self): Biothernostics. P.K. Brastianos: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Bristol-Myer Squibb; Advisory / Consultancy: Genentech-Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Lily; Advisory / Consultancy: TESARO; Advisory / Consultancy: AngioChem. D. Juric: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Syros; Advisory / Consultancy: Ipsen; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Placon Therapeutics. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

319P - The role of AXL as mechanism of resistance to trastuzumab and a prognostic factor in breast cancer HER2 positive: A translational approach (ID 3588)

Presentation Number
319P
Lecture Time
12:00 - 12:00
Speakers
  • Anna Adam-Artigues (Valencia, Spain)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

Breast cancer (BC) is a heterogeneous disease. HER2+ BC represents between 15-30% of cases. Trastuzumab (T), a monoclonal antibody, has been successfully improved clinical benefits in both adjuvant and in metastatic settings. Despite this evidence, many patients experience resistance to therapy. The objective of this study is to assess AXL as a potential mechanism of resistance and its implication as a prognostic factor.

Methods

We used three cell lines with acquired resistance to T. Resistant models were generated by treating parental cells (AU565, SKR3, BT474) with constant dose of T (15mg/mL) for 6 months. Cell viability was estimated by MTT assay. Proteins were assessed by Western blot (WB) and flow cytometry and genes by qRT-PCR. AXL was downregulated by siRNA and a selective AXL inhibitor (TP-0903). The prognostic value of AXL was evaluated in primary tumor in a cohort of HER2+ BC patients treated with T in adjuvant setting from Hospital Clínico València (n = 33).

Results

Acquired resistant cell lines (RCL) maintained HER2 overexpression. Cells were more proliferative and presented an increase in stem cell-like characteristics compared to sensitive parental cell lines. There was an important up-regulation of AXL (>2.5 fold-change) and epithelial-mesenchymal transition markers (VIM, CDH2, and FN1) in RCL (p < 0.05). Sensibility to T was restored by silencing AXL and with TP-0903 treatment decreasing cell viability and IC50 of T (p < 0.05). AXL expression was associated with metastasis in a cohort of HER2+ BC patients (p < 0.001). There was no difference in GAS6 (a ligand of AXL). The role of AXL was also evaluated in a public data set and it was related with worse prognosis (p < 0.001).

Conclusions

Our results suggest: 1) RCL were more proliferative, more mesenchymal-like and stem cell-like properties; 2) AXL was a potential mechanism of secondary resistance to T; 3) Combination therapy with AXL inhibitor plus T restored sensitivity in in vitro model with AXL overexpression; 4) AXL expression was associated with relapse in HER2+ BC patients. These results showed AXL as a prognostic factor and a potential therapeutic target in HER2+ patients with resistance to T.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Lluch: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Celgene. All other authors have declared no conflicts of interest.

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Poster Display session 2 Poster Display session

320P - Untargeted assessment of tumour fractions in plasma for monitoring and prognostication from metastatic breast cancer patients undergoing systemic treatment (ID 5640)

Presentation Number
320P
Lecture Time
12:00 - 12:00
Speakers
  • Marija Balic (Graz, Austria)
Session Name
Poster Display session 2
Location
Poster Area (Hall 4), Fira Gran Via, Barcelona, Spain
Date
29.09.2019
Time
12:00 - 13:00

Abstract

Background

The aim of this study was to assess the prognostic and predictive value of an untargeted assessment of tumor fractions in the plasma of metastatic breast cancer patients and to compare circulating tumor DNA (ctDNA) with circulating tumor cells (CTC) and conventional tumor markers.

Methods

Patients and methods: 29 patients with metastatic breast cancer were included in this single-institution observational cohort study. Blood samples were obtained at first diagnosis of metastases, during several lines of treatment, and/or at every further moment of progression/development of new metastases. We assessed tumor fractions in plasma using an untargeted mFAST-SeqS method. CTCs were captured using a sized-based microfilter and identified as nucleated, cytokeratin positive/CD45 negative cells. Resulting ctDNA z-scores were compared to tumor fractions established with the recently published ichorCNA algorithm and associated with the clinical outcome.

Results

We observed a close correlation between mFAST-SeqS z-scores and ichorCNA ctDNA quantifications. Patients with mFAST-SeqS z-scores above three (34.5%) showed significantly worse overall (p = 0.014) and progression-free survival (p = 0.018) compared to patients with lower values. Elevated z-score values were clearly associated with radiological proven progression. In contrast, baseline CTC count, CEA, and CA15-5 had no prognostic impact on the outcome of pat