Background

MONALEESA-3 demonstrated the efficacy and safety of R+F vs. P+F in PMW women with HR+/HER2- ABC. This exploratory study used data from MONALEESA-3 to estimate quality-adjusted survival outcomes for patients receiving R+F versus P+F in this trial.

Methods

For each treatment arm, Kaplan-Meier overall survival (OS) was partitioned into 3 states: toxicity (TOX) = time spent with grade 3-4 adverse events before disease progression; progression (PROG) = time between disease progression and death; and time without symptoms or toxicity (TWiST) = time not in TOX or PROG. Quality-adjusted time in each state for each arm was calculated by combining the estimated mean time in each state with treatment-group specific health-state utility values (HSUVs) estimated using EQ-5D-5L assessments from MONALEESA-3. Outcomes included quality-adjusted PFS (QAPFS), quality-adjusted OS (QAOS) and Q-TWiST. Q-TWiST was calculated with HSUVs for TOX and PROG defined relative to TWiST.

Results

Mean PFS and OS were significantly greater with R+F vs P+F (difference 0.56 and 0.19 years, respectively). Mean time in TOX and TWiST were greater with R+F, whereas mean time in PROG was greater with P+F. Results were similar for quality-adjusted time in the states. The difference in QAPFS for R+F vs P+F was 0.45 years (95%CI 0.27 to 0.63) greater (p<.0001). QAOS was numerically greater with R+F vs P+F although this difference was not statistically significant (0.16 years, 95%CI 0.07 to 0.45, p=0.0569). Q-TWiST was 0.23 years greater with R+F (95%CI 0.07 to 0.45, p=.0069). In a sensitivity analysis using a published estimate of disutility for PROG, the differences in QAOS was 0.23 years (95%CI 0.08 to 0.41, p=0.0022).

Conclusions

Adding ribociclib to fulvestrant in PMW with HR+/HER2- ABC improves QAPFS, results in clearly clinically important improvements in Q-TWiST and may result in improved QAOS.

Clinical trial identification

CLEE011F2301 / NCT02422615.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

G. Jerusalem: Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Novartis Pharmaceuticals Corporation; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Roche; Honoraria (self), Research grant/Funding (self), Non-remunerated activity/ies: Pfizer; Honoraria (self), Non-remunerated activity/ies: Lilly; Honoraria (self), Non-remunerated activity/ies: Amgen; Honoraria (self), Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Daiichi-Sankyo; Non-remunerated activity/ies: MedImmune; Non-remunerated activity/ies: Merck KGaA. T. Delea: Research grant/Funding (institution): Novartis Pharmaceuticals Corporation. M. Martin Jimenez: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche-Genentech; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Taiho Oncology. M. De Laurentiis: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen. A. Nusch: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: Novartis. J.T. Beck: Research grant/Funding (institution): Novartis Pharmaceuticals Corporation. A. Chan: Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Research grant/Funding (self): Eisai; Honoraria (self): Novartis; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony: Prime Oncology. S-A. Im: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: Hanni; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: MediPacto; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: Lilly. A. Lonshteyn: Research grant/Funding (institution): Novartis Pharmaceuticals Corporation. D. Chandiwana: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. B. Lanoue: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. P. Fasching: Advisory/Consultancy, Research grant/Funding (self): Novartis; Research grant/Funding (self): BionTech; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Celgene; Honoraria (self): Daiichi-Sankyo; Advisory/Consultancy: TEVA; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Myelo Therapeutics; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Puma; Research grant/Funding (self): Cepheid; Advisory/Consultancy: Lilly; Advisory/Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

Background

RIB + FUL improved progression-free survival (PFS) and overall survival (OS) vs placebo (PBO) + FUL in patients (pts) with hormone-receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2−) ABC in ML-3 (NCT02422615). Here we report health-related quality of life (HRQOL) data in 1L and 2L (including early relapsers [ERs]) pts.

Methods

Pts were randomized 2:1 to RIB and PBO groups. HRQOL and pain were evaluated using EORTC QLQ-C30, EQ-5D-5L, and BPI-SF questionnaires. A linear effects model was used to determine least squares (LS) mean change from baseline (BL) in global health status (GHS). Times to definitive 10% deterioration (TTD) were compared between treatment arms using stratified log-rank tests.

Results

Questionnaire compliance rates were >90% at BL for each measure. Numbers of pts to complete questionnaire at cycles 3, 9, 15, and 22 in RIB vs PBO arms were 184 vs 98, 155 vs 80, 121 vs 67, and 102 vs 52, respectively, in 1L pts and 171 vs 67, 124 vs 49, 92 vs 26, and 65 vs 17 in 2L pts. Median TTD results generally favored RIB, including a trend toward GHS benefit especially evident in 1L pts (Table). HRQOL was generally improved from BL in both arms during treatment (data to be presented at congress); at end of treatment (EOT) in 1L pts, both arms showed GHS decrease from BL (LS mean change from BL: −5.2 points with RIB [n=104] vs −4.4 points with PBO [n=76]). In 2L + ER pts, GHS decreased from BL to EOT in both arms (LS mean change: −7.1 [n=139] vs −5.2 [n=67], respectively). Table: 144P

Conclusions

Adding RIB to FUL as 1L or 2L therapy maintained QOL, with increased GHS benefit in 1L pts, although, 2L + ER pts showed consistent TTD benefit across PROs. Some TTD hazard ratios (eg, pain) had wide 95% CIs and must be interpreted cautiously. These results, along with PFS and OS benefits observed with RIB, support use of RIB + FUL as 1L or 2L therapy to treat HR+/HER2− ABC.

Clinical trial identification

CLEE011F2301 / NCT02422615.

Editorial acknowledgement

Editorial assistance provided by Casey Nielsen, PhD of MediTech Media, LLC. Editorial support was funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

P. Fasching: Research grant/Funding (institution): BionTech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): Merck Sharpe and Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): Puma; Research grant/Funding (institution): Cepheid; Honoraria (self), Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self): AstraZeneca; Research grant/Funding (institution): Novartis. G. Jerusalem: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): AbbVie; Honoraria (self): Daiichi-Sankyo; Advisory/Consultancy: MedImmune; Advisory/Consultancy: Merck. J.T. Beck: Research grant/Funding (institution): Novartis. M. De Laurentiis: Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Honoraria (self), Speaker Bureau/Expert testimony: Celgene; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Eisai; Honoraria (self), Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Speaker Bureau/Expert testimony: Amgen; Honoraria (self): MSD. G.V. Bianchi: Honoraria (self): Novartis; Honoraria (self): Eli Lilly. M. Martin Jimenez: Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Roche-Genentech; Honoraria (self): GlaxoSmithKline; Honoraria (self): PharmaMar; Honoraria (self): Taiho Oncology. S. Chia: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Hoffman LaRoche; Honoraria (self), Research grant/Funding (institution): Eli Lilly. A. Gaur: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. M. Sondhi: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. K. Rodriguez-Lorenc: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. B. Lanoue: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. D. Chandiwana: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. A. Nusch: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Amgen. All other authors have declared no conflicts of interest.

Background

Chemotherapy-induced amenorrhea (CIA) has been identified as a prognostic factor for better outcome in luminal breast cancer (BC) patients. Though, it may be associated to menopausal symptoms affecting patients’ quality of life. The aim of this study was to assess patients’ complaints related to CIA.

Methods

We analyzed data of premenopausal patients who received adjuvant chemotherapy then Tamoxifen for stage I-III luminal BC and developed amenorrhea. Perimenopausal patients were not included. CIA was defined as absence of menses for at least 6 months, occuring during chemotherapy or within 3 months after chemotherapy. We searched menopausal symptoms such as: hot flashes, dyspareunia, bone loss, fertility problems and cognitive disorders.

Results

We identified 83 patients with luminal early breast cancer treated with adjuvant chemotherapy followed by tamoxifen. Sixty percent of them experienced CIA (n=50). Thirty-three of these patients had menstruation resumption. We note that all patients received anthracycline based regimen, followed by taxane in 77% of patients. Menopausal symptoms were present in 83% of patients who did not experience menstruations resumption (MR) versus 47% in patients who had MR. Main symptoms were: hot flashes (38%), dyspareunia (33%), reduced libido (22%), and osteopenia in 20% of cases. Osteoporosis was noted in 5 patients. There was no fertility problems due to CIA in our study. Memory lapses occurred in 8% of patients. Although CIA significantly improved outcome in luminal BC patients after a median follow up time of 67 months [18-335] (hazard ratio for Disease-Free Survival was 0.1, 95%CI 0.01-0.30; p<0,001 and hazard ratio for Overall Survival was 0.32, 95%CI 0.07-0.805; p=0.032), the presence or the absence of menopausal symptoms didn’t significantly impact survival in these patients (p=0.5).

Conclusions

Although CIA is now correlated to better outcome in luminal early BC patients, it can alter quality of life attributable to menopausal symptoms. The occurrence of these symptoms didn’t impact prognosis in our study while developing CIA did. Therefore, these symptoms should be screened and treated regularly to improve patients’ satisfaction.

Legal entity responsible for the study

Department of Medical Oncology of the Military Hospital of Tunis: Dr. Ichrak Ben Abdallah and Dr Aref Zribi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Circulating tumor cells (CTC) are associated with clinical outcome in metastatic breast cancer (MBC). We explored the ability of early CTC monitoring (after 2 cycles) for predicting clinical benefit (CB), overall response rate (ORR) and outcome in terms of progression-free survival (PFS) and overall survival (OS) in patients (pts) with HER-2 negative MBC receiving first-line treatment with bevacizumab and paclitaxel.

Methods

Multicenter prospective observational study. Centralized CTC determination was performed at baseline (C0) and after cycle 2 (C2) using CellSearch. A cutoff of 5 CTCs/7.5ml was used to stratify pts into treatment-sensitive (<5 CTCs) and resistant (≥5 CTCs). The optimal CTC level cutoff for predicting CB and PFS was assessed using ROC curves.

Results

111 pts were enrolled: median age: 54 years; ECOG 0/1: 50.5/39.6%; triple-negative: 29%; metastatic sites (median): 3; metastases location: liver (62%), bone (58%), lung (40%). The clinical benefit rate (CBR), ORR, and median PFS for the whole cohort were 65%, 41%, and 16.6 months, respectively. With a median follow-up of 17.5 months, the median OS was not achieved. At C0, 43/87 (49%) and 44/87 (50.6%) pts presented with <5 and ≥5 CTCs, respectively. The CTC level after C2 was in 73/85 (86%) and 12/85 (14%) pts <5 and ≥5, respectively. Among pts with CTCs ≥5 at C0, 78% had <5 CTCs after C2. The CTC level after C2 was predictive for CBR (73% vs 59%, p=0,046), ORR (48% vs 17%, p=0.043), and PFS (17 vs. 5 months, p=0.026). Median OS was 13 months in pts with ≥5 CTCs after C2 and it was not achieved in pts with <5 CTCs (p <0.001). A cutoff point of 1 CTC after C2 yielded 65% sensitivity and 61% specificity for prediction of PFS (p=0.021). Pts with 0 CTC achieved a significantly longer PFS vs. those with at least 1 CTC after 2 cycles (22.6 vs. 8.1 months; p=0.005). Grade 3-4 toxicity rate (39%) was not significantly different according to CTCs after 2 cycles (p =0.531).

Conclusions

CTC monitoring after 2 cycles of first-line bevacizumab-paclitaxel treatment may predict tumor response and clinical outcome in terms of PFS and OS in HER-2 negative MBC.

Editorial acknowledgement

Cristina Vidal, from the CRO (Contract Research Organization) Dynamic Science (Spain) has provided editorial and medical writing support funded by Roche Farma S.A.

Legal entity responsible for the study

Roche Farma S.A.

Funding

Roche Farma S.A.

Disclosure

I. Álvarez-López: Advisory/Consultancy: Roche, Pfizer, Novartis, and Genomic Health; Speaker Bureau/Expert testimony: Pfizer, Novartis, and Roche; Research grant/Funding (institution): Pfizer, Roche, and AstraZeneca; Travel/Accommodation/Expenses: Pfizer, Roche, and Eisai. F. Ayala de la Pena: Speaker Bureau/Expert testimony: AstraZeneca, Celgene, Eisai, Novartis, Roche, Pfizer, Pierre Fabre; Research grant/Funding (institution): Celgene, Roche; Travel/Accommodation/Expenses: Roche, Pfizer, Celgene, Eisai, Pierre Fabre, and MSD. A. Perelló: Advisory/Consultancy: Roche, Pfizer, Novartis, MSD, and Eisai; Speaker Bureau/Expert testimony: Pfizer, Novartis, and Roche; Travel/Accommodation/Expenses: Roche, Novartis. A. Llombart Cussac: Advisory/Consultancy: Lilly, Roche. Pfizer, Novartis, Pierre-Fabre, Genomic Health, and GSK; Speaker Bureau/Expert testimony: Lilly, AstraZeneca, MSD; Leadership role: Eisai, Celgene, Lilly, Pfizer, Novartis, Roche, and MSD; Research grant/Funding (institution): Roche, Foundation Medicine, Pierre-Fabre, Agendia; Travel/Accommodation/Expenses: Roche, Lilly, Novartis, Pfizer, AstraZeneca; Shareholder/Stockholder/Stock options: MedSIR; Initia-Research. All other authors have declared no conflicts of interest.

Background

To describe and characterize cancer-specific health-related quality of life (HRQOL) among patients diagnosed with early stage HR+/HER2- BC.

Methods

A multinational (France, Germany, Italy, Japan, Spain, UK and US) survey of patients diagnosed with stage I-III HR+/HER2- BC was conducted from June to October 2019. Patients were identified by their consulting physician and invited to complete a pen and paper questionnaire. Patients completed the General and Breast version of the cancer-specific Functional Assessment of Cancer Therapy (FACT-G and -B) questionnaires. Mean FACT-G and FACT-B scores (overall and specific subscales) were calculated and compared by disease status (active adjuvant treatment vs. surveillance vs. recurrence) at the time of questionnaire completion using Mann-Whitney and Chi-Squared tests.

Results

1,152 patients completed HRQOL questionnaires (mean age 59 years, treatment status at diagnosis: 76% active adjuvant treatment, 21% surveillance and 3% recurrence). Mean [standard deviation] FACT-G scores (62.2 [16.0]) for the recurrence group were significantly lower than mean scores for disease-free patients in active adjuvant treatment (72.8 [18.3]) or surveillance (71.3 [16.0]) groups. Mean FACT-B scores were also significantly lower for the recurrence group (86.4 [19.5]) compared to active adjuvant treatment (99.4 [22.5]) and surveillance groups (97.7 [19.7]). FACT subscale scores for physical, emotional and functional well-being were also the lowest among the recurrence group (all p-values <0.05).

Conclusions

Group-level differences in cancer-specific HRQOL were statistically significant, with disease-free patients in active adjuvant treatment or surveillance groups reporting higher HRQOL and well-being than patients in the recurrence group. These findings demonstrate the high burden of disease on HRQOL with recurrence among patients with early stage HR+/HER2- BC.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

C. Criscitiello: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer Inc; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli-Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. D. Spurden: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. A. Rider: Full/Part-time employment, Adelphi were paid consultants to Pfizer in connection with the development of this abstract: Adelphi Real World. R. Williams: Full/Part-time employment, Adelphi were paid consultants to Pfizer in connection with the development of this abstract: Adelphi Real World. M. Corsaro: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. J. Pike: Full/Part-time employment, Adelphi were paid consultants to Pfizer in connection with the development of this abstract: Adelphi Real World. E.H. Law: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc.

Background

Genetic counselling and testing are recommended for selected patients with breast cancer (BC). We aimed to asses genetic counselling referral rates in an academic center of patients with BC that fulfilled clinical criteria and/or family history for BRCA status testing.

Methods

In this retrospective study, all patients diagnosed with breast cancer at the Integrated Cancer Care Centre of Charles-Le Moyne Hospital between January 1^st and December 31^st 2017 were included. The clinical characteristics and family history from the patient’s charts were reviewed in order to determine if genetic counselling was indicated according to the NCCN Version 2.2015 of “Clinical practice guidelines in oncology. Genetic/Familial High-Risk Assessment: breast and ovarian” and to assess if the patients were subsequently referred. The main objective was to determine the proportion of patients with BRCA status testing criteria referred for genetic counselling in an academic center.

Results

266 patients diagnosed with BC were included. 81 (30.4%) patients met one or more criteria for BRCA status testing. Among those, 48 (59.2%) were referred for genetic counselling and 33 (40.8%) were not. Among the patients not referred, 11 (33.3%) met clinical criteria and 22 (66.6%) met family history criteria. The family history criteria most often overlooked was of two or more BC diagnoses in close family (15 patients), followed by BC diagnosis of a relative under the age of 50 (4 patients). The clinical criteria of BC diagnosis equal or under the age of 45 was most often missed (6 patients), followed by triple negative BC at age equal or under 60 years in 2 patients. There were also 25 patients which had genetic testing but who did not appear to meet referral criteria (34% of patient of all patients referred).

Conclusions

A lower than expected genetic counselling referral rate of patients meeting criteria for BRCA status testing was observed. A significant number of patients were also referred without meeting testing criteria. These findings support the need to raise awareness and better inform clinicians treating breast cancer patients in order to improve the rates of genetic counselling and testing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Invasive lobular carcinoma (ILC) is the second most commonly diagnosed histological subtype of breast cancer, comprising up to 15% of all cases. Considerable data suggest there are fundamental clinical and biological differences between ILC and the more commonly diagnosed invasive carcinoma no special type. We sought to characterise clinical, pathological and biological parameters that could predict prognosis in ILC that would aid in the understanding of tumour subtype and in the management of patients diagnosed with this subtype of disease.

Methods

Patient cohorts were assembled from the Royal Brisbane and Women’s Hospital and Wesley Hospital, Brisbane, Australia. Clinical and pathology data were obtained from medical records and re-review of radiology (mammography and ultrasound) and pathology features. Clinical follow up data were collected from the Queensland Cancer Registry. Tissue microarrays were constructed from resected specimens in the form of formalin-fixed, paraffin-embedded tumour tissue. Immunohistochemistry (IHC) was performed for a series of putative novel biomarkers predictive of prognosis that were identified during the development of LobSig, a novel gene signature with prognostic potential in ILC.

Results

Features of known prognostic nature in ILC were evident in this cohort (i.e. tumour size, grade and lymph node status). By mammography, most ILC were classified as localised, spiculated lesions (124/260, 48%), while 30% showed no detectable abnormality. ILC were classified by ultrasound as localised (80%) or diffuse (20%) lesions. ILC not detected by mammography were more likely to be patients <50 years and/or with dense parenchyma in the surrounding breast tissue. In both mammography and ultrasound, localised lesions had a significantly better breast cancer specific survival (BCSS) relative to diffuse lesions (p<0.05). Preliminary IHC data indicate the expression of ARGLU, FBXL3 and RNF135 might be associated with BCSS in ILC (p<0.05, Log rank (Mantel-Cox) test).

Conclusions

We illustrate some novel clinicopathological and biological features that contribute to the understanding of ILC as a tumour entity and may aid in the management of patients in the future.

Legal entity responsible for the study

The University of Queensland.

Funding

Wesley Research Institute; National Health and Medical Research Council, Australia; National Breast Cancer Foundation, Australia.

Disclosure

All authors have declared no conflicts of interest.

Background

Recently, poly ADP-ribose polymerases inhibitors (PARPi) in HER2- ABC have become available and international guidelines have broadened the eligibility criteria for gBRCA1/2 testing. We assessed gBRCA1/2 testing patterns among ONC treating HER2- ABC in the US, Israel and France, Germany, Italy and Spain (EU4).

Methods

ONC were recruited to complete an online survey as well as extract data from medical charts for the next 8-10 presenting patients (pts) with HER2- ABC in 2019/2020. gBRCA1/2 testing rates were assessed from medical charts and linked to the ONC survey. Differences in ONC gBRCA1/2 testing patterns by demographics and region (EU4, Israel, US) were compared using t-tests.

Results

2,156 records were provided by 260 ONC [n=214 (82.3%) US, n=24 (9.2%) EU4, n=22 (8.5%) Israel]. Across all regions, significant differences in gBRCA1/2 testing rates by ONC were observed (Table). ONC practicing at an academic medical center vs. community practice were more likely to perform gBRCA1/2 testing [38.0% (SD=37.6) vs 25.3% (SD=31.2) (p = 0.005)]. ONC currently or previously involved in clinical trials were numerically more likely to perform gBRCA1/2 testing compared to ONC who have never been involved in clinical trials 33.6% (SD=35.9) vs 30.3% (SD=39.9) (p=0.567). Table: 157P

ONC gBRCA1/2 Testing patterns

Conclusions

In this analysis, regional differences in gBRCA1/2 testing rates were observed. Significantly lower gBRCA1/2 testing rates were observed among ONC in community practice settings vs academic settings. Given the availability of PARPi, these data highlight the need to increase ONC awareness about gBRCA1/2 testing especially among ONC in community practice and/or with no prior clinical trial experience.

Legal entity responsible for the study

Pfizer.

Funding

Pfizer.

Disclosure

R. Mahtani: Research grant/Funding (self), Research grant/Funding (institution): Genentech; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy: Amgen. A. Niyazov: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. K. Lewis: Full/Part-time employment: Adelphi Real World. R. Wild: Full/Part-time employment: Adelphi Real World. A. Rider: Full/Part-time employment: Adelphi Real World. B. Arondekar: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. M.P. Lux: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: Lilly; Advisory/Consultancy, Advisory boards: MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: Novartis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses, Advisory boards, Honoraria for lectures medical education activities, Travel support: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: Eisai; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: Genomic Health; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Advisory boards, Honoraria for lectures medical education activities: Roche; Honoraria (self), Honoraria (institution), Honoraria for lectures medical education activities: Medac; Honoraria (self), Honoraria (institution), Honoraria for lectures medical education activities: onkowissen.de; Honoraria (self), Honoraria (institution), Honoraria for lectures medical education activities: ClinSol.

Background

Breast cancer is identified as a leading cancer in Kyrgyz females. Poor diagnostic approaches lead to high rate of advanced breast cancer cases and consequently to high mortality rate. Genetic testing is a promising method of prevention and early diagnosis of breast cancer.

Methods

This was a case-control study of 201 women of the Kyrgyz ethnic group with a morphologically verified breast cancer (N=99) and 102 controls age-matched with BC cases. The mean age of the patients was 48 years (minimum 24, maximum 74, STD=9.83). The genotyping was performed by using restriction fragment length polymorphism assay. The extraction of DNA was carried out from venous blood.

Results

Genotype CT of the HMMR V353A polymorphism is associated with low risk of breast cancer in the Kyrgyz females (OR=0,481, 95%CI 0,272 – 0,850, р=0,011). Combination of the allele 194Trp (XRCC1 Arg194Trp) and genotype СТ (HMMR V353A) (OR=0,302, [95% CI 0,128-0,713], р=0,005), combination of genotypes CT (HMMR V353A) //TT (Palb2 T1100T (3300T>G) (OR=0,459, 95% CI [0,259-0,814], р=0,007), combination of genotypes CT (HMMR V353A) //GG (TNF aG3080A) (OR=0,546, 95% CI [0,298-0,999], р=0,048) are also associated with low risk of breast cancer in the Kyrgyz ethnic group. Furthermore, the allele 194Trp is associated with late age of onset of breast cancer when comparing to 194Arg allele of XRCC1 gene (p=0,017). Allele 194Trp significantly more often occurs in postmenopausal women (p=0,005) and in women with high BMI (>25) (p=0,003).

Conclusions

These results may contribute to further genetic research aimed at identifying genes associated with breast cancer in the Kyrgyz population.

Legal entity responsible for the study

Research Institute of Molecular Biology and Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

The SOLAR-1 trial (NCT02437318) demonstrated the efficacy and safety of alpelisib (A) + fulvestrant (F) vs placebo + fulvestrant as first- or second-line (2L) treatment (trt) in postmenopausal women with PIK3CA-mutated (mut), HR+, HER2– ABC. Everolimus + exemestane (E+E) is often used as 2L trt of HR+, HER2– ABC based on the BOLERO-2 trial (NCT00863655). This study was a population-adjusted indirect trt comparison of PFS for A+F vs E+E as 2L trt in patients (pts) with PIK3CA-mut, HR+, HER2– ABC using pt-level data from SOLAR-1 and BOLERO-2.

Methods

Pts who progressed on an endocrine therapy in the metastatic setting in BOLERO-2 with a PIK3CA mutation based on tissue samples were selected to match corresponding pts in SOLAR-1. Selected BOLERO-2 pts were weighted to match on baseline characteristics of pts in SOLAR-1 using average trt effect in the treated inverse probability of trt weighting. Weights were calculated using propensity scores estimated by logistic regression with covariates for age, race, performance status, tumor histology/cytology and grade, number and location of metastatic sites, time since diagnosis/most recent recurrence/metastasis, and receipt of prior chemotherapy in advanced setting. Hazard ratios (HRs) for PFS for A+F vs E+E were estimated by Cox regression with variances based on robust sandwich estimates.

Results

A total of 36 2L pts with a PIK3CA mutation receiving E+E from BOLERO-2 were matched to 79 pts from the corresponding SOLAR-1 2L population. Before weighting, the PFS was statistically significantly higher for A+F vs E+E (HR 0.549, 95% CI, 0.338-0.893, P=0.0157). The results were consistent after weighting, with an HR for PFS of 0.513 (95% CI, 0.263-0.999, P=0.0497).

Conclusions

Analysis of comparable populations from the SOLAR-1 and BOLERO-2 trials suggest A+F may yield clinically and statistically significant improvement in PFS compared with E+E as 2L trt for postmenopausal women with PIK3CA-mut, HR+, HER2– ABC; however, low pt numbers may limit conclusions.

Clinical trial identification

NCT02437318; NCT00863655.

Editorial acknowledgement

Medical editorial assistance was provided by Monica E. Burgett, PhD of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceutical Corporation.

Funding

Novartis Pharmaceutical Corporation.

Disclosure

E.M. Ciruelos: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Reports honoraria from, and consulting, and paid speakers’ bureaus for Novartis, Pfizer, Eli Lilly, Roche, and travel support from Roche and Pfizer. T. Delea: Research grant/Funding (self): Reports research funding and consulting fees from Novartis. I. Mayer: Advisory/Consultancy, Research grant/Funding (self): Reports consulting for Novartis, Genentech, Eli Lilly, AstraZeneca, GSK, Immunomedics, Macrogenics, and Seattle Genetics, and research funding from Novartis, Genentech, Pfizer. J. Park: Shareholder/Stockholder/Stock options, Full/Part-time employment: Reports employment at and stock ownership of Novartis. D. Chandiwana: Full/Part-time employment: Reports employment at Novartis. A. Ridolfi: Full/Part-time employment: Reports employment at Novartis. I. Lorenzo: Full/Part-time employment: Reports employment at and personal fees from Novartis. H.S. Rugo: Research grant/Funding (self), Travel/Accommodation/Expenses: Reports research funding from Pfizer, Merck, Novartis, Eli Lilly, Genentech, OBI, Odonate, Daiichi, Eisai, Seattle Genetics, and Macrogenics, and travel support from Eli Lilly, Mylan, Pfizer, Amgen, Merck, and Puma. All other authors have declared no conflicts of interest.

Background

Breast cancer (BC) is the most common female neoplasm in Poland and worldwide, yet up to 7% of all cases are diagnosed <40 years of age. Increased BC morbidity rate in this age group as well as hopes for late maternity need special attention. Chemotherapy constitutes an important element of complex therapy, but it may lead to fertility impairment. Therefore, it is vital that every woman of reproductive age should be informed about the consequences of oncological treatment and about (onco)fertility preservation techniques prior to therapy, which decrease the fear and improve psychological aspects of QoL.

Methods

The data concerning the number of children and further procreation needs in women (N=70), aged 18-40, diagnosed and treated for early breast cancer at Greater Poland Cancer Center in 2018-2019, were taken from patients’ history by an oncologist before (neo-)adjuvant systemic therapy. According to the patients’ wish, consultation with a specialist in reproductive medicine was provided. Additionally, each patient had genetic studies done.

Results

Out of 70 females, aged 18-40 (mean age 29), 14 (20%) were childless at the time of diagnosis. After being informed about the therapy, prognosis, side effects and oncofertility, 12 patients (17%) decided to have a consultation with a specialist in reproductive medicine; 5 of them (7%) already had children. In 2 women (3%), hormonal stimulation in combination with tamoxifen was used; then, oocytes were collected and cryopreserved. In 20 (29%), gonadotropin analogues were added to (neo-)adjuvant chemotherapy. In 17 patients (24%) pathogenic mutations in BRCA1/2 genes were found.

Conclusions

Oncofertility counselling in young BC patients should be one of the basic elements of complex patient care. High frequency of pathogenic mutations in BRCA1/2 genes in young females should be taken into consideration according to possible childbearing wishes after termination of therapy and before prophylactic oophorectomy.

Legal entity responsible for the study

The authors.

Funding

Greater Poland Cancer Center.

Disclosure

All authors have declared no conflicts of interest.

Background

De novo oligometastatic breast cancer (OMBC) is a rare presentation of advanced stage breast cancer (BC) with ≤ 5 metastatic lesions at diagnosis. Its clinical management is not well defined because of varying definitions, lack of specific biomarkers and lack of dedicated prospective clinical studies. Here, we investigated tumor immune microenvironment, classical clinic-pathological parameters including treatment and correlated them with survival in a cohort of de novo OMBC patients to better characterize this disease entity.

Methods

Clinico-pathological characteristics of 115 de novo OMBC and 117 de novopolymetastatic (PM) patients treated in two cancer centers between 2000 and 2016 were retrospectively collected. Tumor-Infiltrating Lymphocytes (TILs) were quantified (n=54) and immune subsets were characterized using multiplex multispectral immunohistochemistry (n=31). Survival analyses were performed using Cox regression models.

Results

De novo OMBC was associated with more Luminal B and less Luminal A subtypes (as defined by IHC), lower LDH and CA 15-3 levels compared to PM patients. Most OMBC patients were first treated with systemic therapy (66.1%), mainly by chemotherapy (71%) followed by surgery. Patients treated with upfront surgery (33.9%) received pseudo-adjuvant systemic therapy (92.3%). OMBC had better survival than PM with median progression-free and overall survival of 23.9 and 50.4 months respectively. Surgery of the primary tumor before 1^stprogression, the use of poly-chemotherapy and a lower histological grade were associated with a better outcome in de novo OMBC. These breast tumors showed low immune infiltration (median TIL levels 5% (0 – 60%)) with 50% of the cases defined as “cold” tumors. Median CD4 T cell, CD68 macrophage and CD8 T cell infiltration in primary tumors were 8%, 5% and 4% respectively. Interestingly, CD8 T cell level was associated with a better survival.

Conclusions

De novo OMBC is a specific subset of metastatic BC with distinct clinico-pathological characteristics and favorable outcome. An “aggressive” multimodal therapeutic strategy should be considered in this disease entity. We report limited TIL infiltration but revealed the importance of specific tumor immune-infiltrates that should be further investigated.

Legal entity responsible for the study

The authors.

Funding

Les Amis de l'Institut Bordet.

Disclosure

L. Buisseret: Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony: BMS. All other authors have declared no conflicts of interest.