Background

monarchE demonstrated that adjuvant abemaciclib (oral CDK4 & 6 inhibitor)+endocrine therapy (ET) significantly improves invasive disease-free survival (IDFS) in HR+, HER2- high-risk early breast cancer (EBC) compared to ET alone. Here, we report the primary outcome (PO) efficacy and safety data in patients (pts) located in Asia (mainland China, Hong Kong, Japan, Korea, Singapore, and Taiwan), comprising 1,155 (20.5%) of the 5,637 pts of the intent-to-treat (ITT) population.

Methods

Pts with HR+, HER2-, high risk EBC were randomized 1:1 to abemaciclib+ET or ET alone and stratified by prior treatment (txt), menopausal status, and region (North America/Europe; Asia; Other). Exploratory analyses were conducted among pts enrolled from Asia, (median follow-up: ∼19 months in both arms).

Results

In total, 75 IDFS events were observed in pts from Asia (33 in abemaciclib+ET; 42 in ET alone). Abemaciclib+ET demonstrated numerical benefit in IDFS, reflecting a 22.3% reduction in the risk of developing invasive disease [HR (95% CI) = 0.777 (0.493, 1.227)]. Two-year IDFS rates were 93.2% in abemaciclib+ET and 90.1% in ET alone. There was also a numerical improvement in distant relapse free survival (DRFS) [HR (95% CI) = 0.758 (0.455, 1.264)], with 2-year DRFS rates of 94.4% vs 91.7%. The median txt duration of abemaciclib was 17.7 months. In the abemaciclib arm, the most frequent adverse event (AE) was diarrhea (89.5%), most were G1/2 (55.8%/28.7%). More G≥3 AEs and serious AEs were observed with abemaciclib+ET vs ET (53.5% vs 10.5% and 12.1% vs 6.3%), with neutropenia (31.5%) being the most frequent G≥3 AE. Interstitial lung disease occurred in 6.6% pts, G≥3 in 0.3% pts. G≥3 ALT and AST increases occurred in 4.2% and 3.1% pts, respectively.14.5% of abemaciclib-treated pts discontinued abemaciclib or all txt due to AEs.

Conclusions

In pts from Asia with HR+, HER2-, high-risk EBC, abemaciclib plus standard adjuvant ET led to a clinically meaningful improvement in IDFS and DRFS, consistent with benefits demonstrated in the ITT population. Safety was consistent with the known safety profile of abemaciclib. Abemaciclib is the first CDK4 & 6 inhibitor to demonstrate effective and tolerable txt in pts with high-risk EBC, including pts from Asia.

Clinical trial identification

NCT03155997.

Editorial acknowledgement

Eglantine Julle-Daniere.

Legal entity responsible for the study

Eli Lilly.

Funding

Eli Lilly.

Disclosure

Y-S. Yap: Advisory/Consultancy, Personal fees/non-financial support: Eli Lilly; Advisory/Consultancy, Personal fees/non-financial support: Novartis; Advisory/Consultancy, Personal fees/non-financial support: Pfizer; Advisory/Consultancy, Personal fees/non-financial support: AstraZeneca; Advisory/Consultancy, Personal fees/non-financial support: Eisai; Advisory/Consultancy, Personal fees/non-financial support: Roche; Advisory/Consultancy, Personal fees/non-financial support: MSD; Advisory/Consultancy, Personal fees: Inivata. S-B. Kim: Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi-Aventis; Research grant/Funding (self): DongKook Pharm Co. Y. Sagara: Honoraria (self), Personal fees: Eli Lilly; Honoraria (self), Personal fees: Pfizer; Honoraria (self), Personal fees: AstraZeneca. S. Sherwood: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. R.E. McNaughton: Full/Part-time employment: Eli Lilly. R.J. Wei: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. M. Toi: Honoraria (self), Research grant/Funding (self): Chugai, Takeda, Pfizer, Taiho, Eisai, AstraZeneca, Eli Lilly, Shimadzu, Yakult; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Kyowa-Kirin; Research grant/Funding (self): JBCRG association; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Daiichi Sankyo; Honoraria (self): MSD; Honoraria (self): Exact Science; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: Konica Minolta; Research grant/Funding (self): Astellas; Honoraria (self), Advisory/Consultancy, Honoraria for an advisory meeting: BMS; Honoraria (self), Research grant/Funding (self), Research Fund and Honoraria for lecture: Nippon Kayaku; Research grant/Funding (self): AFI technologies; Advisory/Consultancy: Athenex Oncology, Bertis, Terumo, Kansai Medical Net; Advisory/Consultancy, Research grant/Funding (self): Luxonus; Research grant/Funding (self): Shionogi; Research grant/Funding (self): GL Science; Officer/Board of Directors, Board of directors: JBCRG association, Organisation for Oncology and Translational Research, Kyoto Breast Cancer Research Network. All other authors have declared no conflicts of interest.

Background

Abemaciclib is an oral cyclin-dependent kinase 4 & 6 inhibitor, dosed on a continuous schedule, approved for the treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) combined with ET. In this pt population, CR is rarely seen with ET alone. Pt/disease characteristics may correlate with response to a specific treatment. In this post-hoc exploratory analysis, we report characteristics of pts with CR to abemaciclib+ET in M2 and M3.

Methods

M2 (NCT02107703) and M3 (NCT02246621) were double-blind, phase III studies in which women with HR+, HER2- ABC were randomised to receive abemaciclib/placebo+ET (M2: fulvestrant; M3: aromatase inhibitor). M2 included pts with progression during or ≤1 year of (neo)adjuvant ET or on first ET for ABC. M3 included pts who had not received prior systemic therapy for ABC. Disease characteristics were described in pts who achieved CR (RECIST v1.1) across the two studies, focusing on parameters reported to be associated with poor prognosis. Data are from the final progression-free survival analyses.

Results

Of 774 pts randomised to receive abemaciclib in M2 and M3, a total of 23 achieved CR: 14/446 in M2 and 9/328 in M3 (corresponding data in M2 and M3 pts receiving placebo+ET: 1/223 and 1/165 pts, respectively). A total of 3/14 M2 and 6/9 M3 abemaciclib pts had Eastern Cooperative Oncology Group (ECOG) status 1 (remainder: ECOG 0); 2/14 M2 and 0/9 M3 pts were progesterone receptor negative; 4/14 M2 and 3/9 M3 pts had a high-grade tumour; 10/14 M2 and 9/9 M3 pts had no bone-only disease, and 2/14 M2 and 0/9 M3 pts had liver metastases at baseline. Treatment-free interval was <3 years for 3/4 M3 pts with recurrent metastatic disease who had received adjuvant ET. 10/14 M2 pts and 5/9 M3 pts achieved CR <3 months after starting treatment; 7/14 M2 and 6/9 M3 pts had duration of response >15 months.

Conclusions

A small proportion of pts with recurrent ABC treated with abemaciclib in M2 and M3 achieved CR, including some pts with disease characteristics reported to be associated with poor prognosis. Those responses had a short time to onset and were relatively durable.

Editorial acknowledgement

Medical writing assistance was provided by Gill Gummer and Caroline Spencer (Rx Communications, Mold, UK).

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Funded by Eli Lilly and Company.

Disclosure

J. Huober: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self): Hexal; Honoraria (self), Advisory/Consultancy: Eli Lilly and Company; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Daiichi; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self): Eisai; Honoraria (self), Advisory/Consultancy: AbbVie. N. Chouaki, C. Stoffregen, A. Korfel: Full/Part-time employment: Eli Lilly and Company. F. Lerebours: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly and Company; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pierre Fabre; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.

Background

Abemaciclib is approved for HR+/HER2- metastatic breast cancer in combination with endocrine therapy (ET). We evaluated safety and efficacy of abemaciclib in association with ET in a single-institution cohort.

Methods

Patients with HR+/HER2- metastatic breast cancer treated with abemaciclib in combination with ET as first or second line between April 2019 and November 2020 at Istituto Oncologico Veneto of Padova were identified. Clinicopathological characteristics, adverse events and their grade (according to CTCAE 5.0 criteria) were collected. Objective response rate (ORR) according to RECIST 1.1 was also evaluated.

Results

72 patients were included: 52 received abemaciclib as first line, 20 as second line; in 49 patients abemaciclib was administer in combination with an aromatase inhibitor, in 23 with fulvestrant. 95.8% of patients experienced at least one adverse event. The most common was diarrhea (79.2%), mainly G1 (66.7% of cases). Other common toxicities were: neutropenia (56.9%), increased serum creatinine (38.9%), anemia (37.5%), nausea (34.7%), fatigue (23.6%) and hypertransaminasemia (22.2%). Toxicities were mainly low grade; 10.1% of adverse events where G3-4. 48.6% of patients required a temporary interruption of abemaciclib and 45.8% a dose reduction. All 17 patients aged ≥70 required a dose reduction. A concomitant palliative radiotherapy was administered in 16 patients: in all cases radiotherapy was regularly completed; a temporary interruption of abemaciclib was required in 3 patients due to hematologic toxicities. In patients with measurable disease, ORR was 55.7%, significantly higher in first line compared to second line (70.5% vs 17.7%, p<0.001). ORR was not significantly different between full and reduced dose (46.9% vs 65.5%, p=0.143). At the time of the present analysis, 51 patients are still on therapy. Treatment discontinuations were due to disease progression in 17 patients, and to adverse events in 4 (G3 increased ALT in 1 patient and persistent G2-3 cutaneous toxicity in 3 patients).

Conclusions

In a real-world population, abemaciclib was associated with a meaningful rate of objective response, with a favourable safety profile. Side effects were mostly low grade, manageable with temporary interruptions or dose reductions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M.V. Dieci: Honoraria (self): Eli Lilly; Honoraria (self): Genomic Health; Honoraria (self): Novartis; Honoraria (self): Celgene. G. Griguolo: Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Daiichi Sankyo. V. Guarneri: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Eli Lilly; Honoraria (self): MSD. All other authors have declared no conflicts of interest.

Background

Approximately 50% of HER2-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting in order to better establish the bases for clinical recommendations in HER2-positive disease.

Methods

We conducted a literature search up to May 2020 in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI).

Results

Six RCTs (n=5,390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P=0.96). After omitting the ALTTO trial because it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P=0.81).

Conclusions

Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Multigene assays (MGAs) can reduce over and under-treatment with adjuvant chemotherapy in oestrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) early breast cancer. The cost of treatment of early breast cancer and distant recurrence of breast cancer are important parameters in the economic evaluation of MGAs. The recent approval of new treatments in the UK, such as CDK4/6 inhibitors, is likely to increase the cost of management of breast cancer. This study aimed to estimate the cost of adjuvant chemotherapy in early breast cancer and the cost of treating distant recurrence in the UK using expert opinion and published sources.

Methods

A survey of breast cancer specialists in the UK was conducted to identify the distribution of adjuvant drug treatments used in early breast cancer and distant recurrence of breast cancer. The weighted average of clinician questionnaire responses was combined with estimates of length of treatment and drug unit costs from published studies to estimate the weighted mean cost by type of treatment and setting. The analysis was conducted from a UK healthcare cost perspective and included drug list prices, cost of administration and supportive treatments.

Results

The weighted average 6-monthly cost of treatment in early breast cancer and distant recurrence (in 2020 Pound Sterling) is reported in the table. Table: 61P

Summary of cost estimates by treatment

Conclusions

Adjuvant chemotherapy represents a substantial use of scarce healthcare resources in the UK and differs by nodal status. The cost of distant recurrence may be considerably higher than estimates reported in previous studies, which was partly driven by the use of effective, but costly new treatments. The use of the Oncotype DX® Breast Recurrence Score test to guide chemotherapy is likely to result in cost savings by avoiding over-treatment with chemotherapy and avoiding distant recurrence through targeted treatment of patients with a high genomic risk score.

Legal entity responsible for the study

The authors.

Funding

Exact Sciences.

Disclosure

V. Berdunov, J. Griffin: Research grant/Funding (institution): Exact Sciences. S. Millen, A. Paramore, S. Reynia, N. Fryer, N. Georges: Full/Part-time employment: Exact Sciences.

Background

In Mexico, breast cancer (BC) is the leading cause of cancer death in women over 25 years old. Access to genomic platforms for biological intrinsic subgroups identification is not covered by the public health system. Within early BC (EBC) RH+/HER2- the non-luminal subgroup is associated with poor oncologic outcomes.

Methods

A retrospective review of 580 consecutive records of a BC prospective cohort attendeding INCMNSZ during the period Jan-2011 to Jun-2019. A combined score based on ER, PR and Ki67 levels was calculated. NOLUS formula was derived: −0.45^∗ER −0.28^∗PR +0.27^∗Ki67 + 73.02. High-NOLUS cutoff point ≥ 51.38 identified non-luminal population and low NOLUS < 51.38. The model was tested in EBC to identify the frequency of the non-luminal subtype.

Results

Luminal subtype 65.9%, triple negative 17.7%, HER2+ 16.4%. St Gallen classification: luminal A 58.3%, luminal B 33.8%, luminal B HER2+ 7.9%, Within the RH+/HER2- subgroup (n 175) low-NOLUS was 90.3%, and high-NOLUS 9.7%. Tumor grade was G1 37.7%, G2 49.7%, G3 12.6%. 63.9% of the patients with low-NOLUS had luminal A and 36.1% were luminal B. 5.9% of patients with high-NOLUS had luminal A vs 94.1% luminal B (p=<0.001). 82.3% received surgical treatment as initial strategy, neoadjuvant (n 31) 17.7%, (22 chemotherapy, 9 endocrine therapy). None of the patients presented pathologic complete response. Chemotherapy was received in 54.9%, endocrine therapy 95.4%. Median follow-up was 35.5 months, disease-free survival (DFS) of the entire cohort was 95.4% and cancer-specific survival (CSS) 97.1%. Relapse occurred in 4.6% (8/175). Distant recurrence (DR) in 7, all in the high-NOLUS group. DFS for low-NOLUS was 98.1% vs 70.6% high-NOLUS (p=<0.005). CSS for low-NOLUS was 98.1% vs high-NOLUS 88.2% (p=<0.044).

Conclusions

The frequency of the non-luminal subgroup in Mexican patients with EBC RH+/HER2- represented by high-NOLUS is similar to that reported in the literature. Patients with high-NOLUS have worse outcomes in DR and CSS. The NOLUS model is useful to identify non-luminal subgroups in RH+/HER2- EBC in the absence of genetic platforms.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Symptomatic breast cancers share aggressive clinico-pathological characteristics compared to screen-detected breast cancers. The decision to administer adjuvant chemotherapy for early hormone receptor positive (HR+) HER-2 negative (HER2-) breast cancer patients, is guided by both the genomic and the clinical risk of disease recurrence. We assessed the association between the method of cancer detection and genomic and clinical risk, and its effect on adjuvant chemotherapy recommendation.

Methods

Patients with early HR+ HER2- breast cancer, and known OncotypeDX Breast Recurrence Score (RS) test were included. A natural language processing (NLP) algorithm was used to identify the method of cancer detection. The clinical and genomic risks of symptomatic and screen-detected tumors were compared.

Results

The NLP algorithm identified the method of detection of 401 patients, with 216 (54%) diagnosed by routine screening, and the remainder secondary to symptoms. The distribution of OncotypeDX RS varied between the groups. In the symptomatic group there were lower proportions of low RS (13 vs 23%) and higher proportions of high RS (24 vs. 13%) compared to the screen-detected group (p=.03). Symptomatic tumors were significantly more likely to have a high clinical risk (59 vs 40%; p<.0001). Based on genomic and clinical risk and current guidelines, we found that women aged 50 and under, with symptomatic cancer, had an increased probability of receiving adjuvant chemotherapy recommendation compared to women with screen-detected cancers (57 vs. 35%; p=.03).

Conclusions

We demonstrated an association between the method of cancer detection and both genomic and clinical risk. Symptomatic breast cancer, especially in young women, remains a poor prognostic factor that should be taken into account when evaluating patient prognosis and determining adjuvant treatment plans.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I. Wolf: Speaker Bureau/Expert testimony, Research grant/Funding (self): BMS; Speaker Bureau/Expert testimony, Research grant/Funding (self): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis. A. Sonnenblick: Advisory/Consultancy: Eli lilly; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Teva; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Medison; Speaker Bureau/Expert testimony: Roche; Research grant/Funding (self): Novartis; Research grant/Funding (self): Roche. All other authors have declared no conflicts of interest.

Background

The use of VAE for high-risk lesions remains controversial and guidelines are ambiguous. In this study we evaluate and demonstrate how the introduction of VAE impacts the management and clinical outcomes of benign and high-risk lesions in our hospital.

Methods

A retrospective database cohort study was conducted to compare the available operation room time, and excision, re-excision, recurrence, complications and upgrading rates before and after the introduction of VAE. All patients treated for a benign or high-risk lesion in the period from January 2016 up to 2019 were included in the study. To demonstrate the difference in treatment the results for VAE and surgical excision (SE) in the after group were presented separately.

Results

A total of 319 lesions were excised in our hospital during the study period, of which 118 were excised through VAE. The proportion of excised lesions was comparable in the before and after group, but the proportion of SE decreased since the introduction of VAE. High-risk lesions were significantly more often treated with SE than VAE due to the high rate of surgically excised papillary lesions. Recurrence, re-excision and complication rates were comparable in the before and after group. Nearly all malignancies found after excision through VAE or SE were good differentiated in situ carcinoma, and no malignancies were detected during the follow-up of benign and high-risk lesions.

Conclusions

The introduction of VAE reduced OR time for benign and high-risk lesions, implicating that more OR time was available for malignant lesions. Re-excision, recurrence and upgrade rates remained low and could possibly be further reduced by better informing the patient prior to the procedure. This study contributes to the accumulating evidence for the wider deployment of VAE as a treatment option for all high-risk lesions.

Legal entity responsible for the study

Franciscus Gasthuis en Vlietland.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In the primary analysis of the neoadjuvant phase of the FeDeriCa study (NCT03493854; Tan AR, et al. Lancet Oncol 2021), PH FDC SC cycle 7 P + H serum trough concentrations were non-inferior to intravenous (IV) P + H, with comparable total pathological complete response rates and safety profiles. We present updated descriptive safety data that span the adjuvant phase of the study, with an additional 12 months beyond the primary analysis.

Methods

Patients (pts) with HER2-positive operable, locally advanced or inflammatory stage II–IIIC BC and left ventricular ejection fraction (LVEF) ≥55% were randomised 1:1 to eight neoadjuvant chemotherapy cycles (investigator’s choice between two standard regimens) + P IV (loading dose 840 mg, maintenance 420 mg) + H IV (8 mg/kg → 6 mg/kg) or chemotherapy + PH FDC SC (1200 mg P/600 mg H → 600 mg each as FDC SC) every 3 weeks during cycles 5–8. After surgery, pts continued adjuvant HER2-targeted treatment only, as randomised, to complete 18 cycles. Safety was assessed by NCI-CTCAE v4.

Results

Clinical cut-off was 10 July 2020. Adverse events (AEs) are shown in the table; the most common were diarrhoea, radiation skin injury and arthralgia. Infusion-/administration-related reactions within 24 hours were higher with PH FDC SC (17%) than with P + H IV (5%), all grade 1/2 and mostly due to local injection site reactions. No grade ≥3 anaphylaxis/hypersensitivity was reported in either arm. Table: 46P

Conclusions

Overall safety and tolerability, including cardiac safety, of PH FDC SC in the adjuvant phase of FeDeriCa remained comparable to P + H IV, with the exception of AEs associated with the different routes of administration. Results are in line with the expectation that most AEs with PH FDC SC or P + H IV are observed during concomitant chemotherapy.

Clinical trial identification

NCT03493854 (WO40324), 2 Feb 2018.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Funding

F. Hoffmann-La Roche Ltd., Basel, Switzerland.

Disclosure

S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Hanmi, GSK, Lilly, MSD, Novartis, Roche, Pfizer; Research grant/Funding (institution), Investigator-initiated clinical trial research grant through institution: AstraZeneca, Eisai, Daewoong Pharm, Roche, Pfizer; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A.R. Tan: Honoraria (self): Genentech, Novartis, Immunomedics, Celgene, AbbVie, Athenex, G1 Therapeutics, Eisai, Merck; Research grant/Funding (institution), Institutional clinical trial support: Roche/Genentech, Pfizer, Merck, Tesaro; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Mattar: Advisory/Consultancy, Advisory board consultant: Roche, Novartis, Pierre Fabre, AstraZeneca, Exact sciences; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. R. Colomer: Honoraria (self): Roche, Eli Lilly, MSD, AstraZeneca; Research grant/Funding (institution): Roche, Lilly, MSD, BMS, AstraZeneca, Pfizer, Novartis; Non-remunerated activity/ies: Roche, MSD; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. D. Stroyakovskii: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. Z. Nowecki: Travel/Accommodation/Expenses: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. De Laurentiis: Honoraria (self), Speaker’s honoraria and advisory board honoraria: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Advisory/Consultancy: Pfizer, Novartis, Roche, Celgene, AstraZeneca, Eisai, Lilly, Amgen, MSD, Pierre Fabre, Genomic Health, Daiichi Sankyo; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. J-Y. Pierga: Honoraria (self): Roche, AstraZeneca, Pfizer, Amgen, Novartis, Exact Sciences, Seagen, Lilly, Pierre Fabre, MSD; Honoraria (institution): BMS, Roche, MSD, Eisai, Novartis, Sanofi; Speaker Bureau/Expert testimony: Daiichi Sankyo; Research grant/Funding (institution): Servier, Roche, Menarini Silicon Biosystems; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. K.H. Jung: Honoraria (self), Advisory board honoraria: Roche, Novartis, AstraZeneca, Takeda, Celgene; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Schem: Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Aguila: Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. T. Badovinac Crnjevic: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. S. Heeson: Shareholder/Stockholder/Stock options: Roche; Licensing/Royalties, Issued patent (fixed-dose combination of pertuzumab and trastuzumab): Roche; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. M. Shivhare: Shareholder/Stockholder/Stock options: Roche Products Limited; Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. A. Alexandrou: Full/Part-time employment, Full-time: Roche Products Limited; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. E. Restuccia: Shareholder/Stockholder/Stock options: Roche; Full/Part-time employment, Full-time: Roche; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche. C. Jackisch: Honoraria (self): AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Advisory/Consultancy: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Research grant/Funding (institution): Roche, Exact Sciences; Travel/Accommodation/Expenses: AstraZeneca, Roche, Lilly, Novartis, Exact Sciences, Pierre Fabre; Non-remunerated activity/ies, Support for third-party writing assistance, furnished by Daniel Clyde, PhD, of Health Interactions: Roche.

Background

Mammography screening reduces breast cancer mortality by 20-40%, but a large proportion of breast cancers are detected at later stages or as interval cancers. The KARMA model was developed that identifies women who are likely to be diagnosed with breast cancer before or at the next mammography screen.

Methods

The study was based on the prospective screening cohort KARMA including 70,877 participants. The study included 974 incident cancers and 9,376 healthy individuals from the cohort. We developed an image-based risk score based on mammographic features (density, masses, microcalcifications), their left-right asymmetries, and age. A lifestyle extended score also included menopausal status, family history of breast cancer, body-mass-index, hormone replacement therapy, and use of tobacco and alcohol. A genetic extended score was also developed including a polygenic risk score including 313 single nucleotide polymorphisms in addition to the image and lifestyle factors. Relative risks were estimated using logistic regression. Tumor sub-type specific risks were also estimated. Absolute risks were estimated based on relative risks, national incidence rates, and competing mortality risk.

Results

The image-based model area under the curve (AUC) was 0.73 (95% CI 0.71,0.74). The lifestyle and genetic extended model AUCs were 0.74 (95% CI 0.72,0,75) and 0.77 (95% CI 0.75,0.79) respectively. There was a relative 8-fold difference in risk between the women at high and general risk. High risk women were more likely diagnosed with large tumors. The image-based model was validated in two external cohorts.

Conclusions

Three mammographic features and their left-right asymmetries generated the basis of the model. The model could optionally be extended with lifestyle factors, family history, and a polygenic risk score. The models identified women at high likelihood of being diagnosed with breast cancer within two years of a negative screen who possibly are in need of supplemental screening or preventive intervention.

Legal entity responsible for the study

Karolinska Institutet.

Funding

Hans and Märit Rausing.

Disclosure

All authors have declared no conflicts of interest.

Background

Receptor subtypes of breast cancer, as defined by immunohistochemistry, are surrogates for molecular subtypes. Despite new emerging molecular tumour classifications, these receptor subtypes are well-known independent predictors of breast cancer death and remain widely used in clinics. Few studies have disentangled the combined influence of receptor subtypes, grade, size (T) and nodal status (N) on breast cancer survival in large groups of recently treated patients.

Methods

From the Cancer Registry of Norway, we obtained detailed clinical information on 24137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015. Of these, 17204 had non-metastatic breast cancer with known receptor status. Receptor subtype was defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Hazard ratios for breast cancer death up to 13 years after diagnosis were estimated using flexible parametric survival models and comparing combinations of receptor subtype, grade and TN status with adjustments for age, year and surgery type. Additional adjustment for adjuvant treatment was done on a subset of women with known treatment information.

Results

Receptor subtype, grade and TN status were strong predictors for breast cancer death, both independently and in combination. The combined effect of all factors was a 20- to 40-fold higher breast cancer mortality rate when comparing to women with the best outcome (ER+PR+HER2-, low grade, T1N0). In women with ER+HER2- subtypes and no nodal spread, a larger tumour size was associated with a significantly higher risk of breast cancer death. Women with ER+HER2- tumours also had an increased late (>5 years) mortality which was largely explained by intermediate/high grade and nodal spread. Women with ER+PR-HER2-, high grade, N+ tumours had particularly high mortality similar to triple negative breast cancer.

Conclusions

These results highlight the importance of thoroughly combining well-known tumour factors to describe the wide range of risks of dying from breast cancer, also among small, node negative tumours.

Legal entity responsible for the study

Cancer Registry of Norway.

Funding

Norwegian Cancer Society under Grant 161326.

Disclosure

All authors have declared no conflicts of interest.

Background

In this study we will, compare VAE with surgical excision for the treatment of benign and high risk lesions, regarding cosmetic outcome and direct health care costs.

Methods

This was a retrospective cohort study, data was collected from electronic patient files in the period between January 2016 and December 2019. VAE was introduced in our hospital (a large teaching hospital) as a treatment for benign and high-risk lesions in July 2017. Cosmetic outcome was measured with the BCTOS cosmetic subscale and presented as an unweighted mean score. Health care costs were presented as mean (SD) and the difference between the two groups (VAE or SE).

Results

Between January 2016 and December 2018, 280 patients were treated for 329 benign or high-risk lesions in our hospital. The initial procedure was a VAE in 104 patients. Mean cosmetic outcome score was not significantly different for VAE (mean 1.54, SD 0.45) compared to SE (mean 1.51, SD 0.45) (p = 0.544). If patients were initially treated with VAE, the total costs of treatment were lower than when patients were initially treated with SE (mean difference € 2527,81). The biggest differences in costs were seen in the procedural and procedure related costs. Even after correcting for tumor size, the number of resected tumors per patient, the number of procedures per patient, the presence of complications, BI-RADS category and the follow-up time, the difference between VAE and SE remained significant (β = -0.65, p < 0.001). All but one of the patients that underwent both VAE and SE preferred VAE over SE, due to the less invasive character of the treatment.

Conclusions

This is the first study in which the cosmetic outcome and direct health care costs of VAE and surgical excision are compared. Health care related costs are significantly lower for patients initially treated with VAE without compromising cosmetic outcome. The health care costs of patients undergoing surgical resection were more than double the costs of patients undergoing a VAE. Implicating that if VAE would be used in more high-risk lesions possibly resulting in more surgical re-excisions due to upgrading of the lesions, VAE might still be cost-effective.

Legal entity responsible for the study

Franciscus Gasthuis & Vlietland.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.