285P - Treatment patterns and clinical outcomes of germline BRCA mutation (gBRCAm)-associated breast cancer (BC): A matched, case-control study

Background

Up to 10% of early BC occur in gBRCAm carriers. Whether gBRCAm-related and sporadic BC have different outcomes is controversial.

Methods

Consecutive patients (pts) who underwent surgery for BC at Dana-Farber Brigham Cancer Center between 1/2016 and 8/2021 and had known gBRCA status were included. gBRCAm cases were matched 1:3 with non-gBRCAm controls by age groups, stage, hormone receptor (HR) status and year of diagnosis. HER2-negative BC were excluded. Clinicopathologic features, treatments, and outcomes of gBRCAm carriers and non-gBRCAm controls were compared.

Results

We identified 189 gBRCAm (107 BRCA1, 82 BRCA2) carriers and 567 matched non-gBRCAm controls. Median age was 43 years (yrs) in carriers and 46 yrs in controls. Most pts had stage I (41.7%) or II (44.7%) BC; 55% of BC were HR+ (38 in gBRCA1m, 66 in gBRCA2m; 312 in non-gBRCAm). Compared to controls, gBRCAm carriers had higher tumor grade (p<0.001), higher recurrence score in HR+ (median 25 vs 19, p<0.001), were more likely to receive chemotherapy (CT) (81 vs 67.4%, p<0.001), including platinum-based regimens (17.6 vs 9.2%, p=0.007). 11 gBRCAm carriers and 3 controls received PARPi. At a median follow up of 42.3 months, invasive disease-free survival (iDFS) and relapse-free survival (RFS) did not differ between gBRCAm and controls after adjusting for age, grade, and CT administration (Table). In triple-negative BC (TNBC), risk of relapse was lower for gBRCAm vs controls (p=0.025). Table: 285P

Conclusions

Pts with BRCA-associated BC have higher-risk pathologic features and are more often treated with CT compared to matched non-gBRCAm BC. After adjusting for treatment and clinicopathologic variables, short-term outcomes did not differ in gBRCAm carriers vs controls overall. However, in TNBC pts, risk of relapse was significantly lower among carriers than controls. Our results provide risk estimates for gBRCAm carriers that could inform the design of future clinical trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck, BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Coordinating PI, Gillead provides clinical trial support to my institution for a study that I am the PI on: Gillead; Financial Interests, Personal, Steering Committee Member: Roche/Genentech, BMS; Non-Financial Interests, Member of Board of Directors: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. T.A. King: Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Invited Speaker: Exact Sciences. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Coordinating PI, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Member of Board of Directors, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. A.H. Partridge: Financial Interests, Personal, Royalties, Royalties received for authorship of Breast Cancer Survivorship section: UpToDate; Non-Financial Interests, Leadership Role, co-Chair of Breast Committee: Alliance for Clinical Trials, National Cancer Institute; Non-Financial Interests, Other, Board of Directors, Member 2022-2026: ASCO. N.U. Lin: Financial Interests, Personal, Advisory Board, Ad board participation: Seattle Genetics, Daiichi Sankyo, Prelude Therapeutics; Financial Interests, Personal, Advisory Board, Ad board/Steering Committee participation; consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Denali Therapeutics, Blueprint Medicines, Janssen, Affinia Therapeutics; Financial Interests, Personal, Advisory Board, Ad board/Steering committee participation: Olema Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory Board: Atera Inc.; Financial Interests, Personal, Royalties, Royalties for book chapter(s): Up to Date; Financial Interests, Institutional, Funding, Trial funding to institute (and steering committee): Olema Pharmaceuticals, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Funding, Trial funding to institute: Zion Pharmaceuticals; Financial Interests, Institutional, Funding, trial funding to institute: Pfizer, Genentech. J.E. Garber: Financial Interests, Personal, Advisory Board: The James P. Wilmot Foundation , Inc., Helix; Non-Financial Interests, Personal, Advisory Board: Earli Inc.; Financial Interests, Institutional, Funding: Invitae Genetics, Myriad Genetics, Ambry Genetics. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma, ARC Therapeutics, Daiichi Sankyo, Eisai, Genentech/Roche, Gilead, Novartis, Sanofi, SeaGen; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Personal, Advisory Board, Ad board participation: Artios, Incyte Corp, BeyondSprings; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Advisory Board participation: Bayer, Infinity Therapeutics, Myovant, OncXerna, Umoja Biopharma, Zentalis, Zetagen; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Ellipses Pharma, Mersana Therapeutics; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Steering Committee Member: CytomX. F. Lynce: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca; Financial Interests, Personal, Invited Speaker: ION; Other, Institutional, Principal Investigator: AstraZeneca, CytomX, Cyclacel, Genentech, Eisai, Incyte. All other authors have declared no conflicts of interest.