Abstract 160P
Background
Breast cancer (BC) in young women is often associated with germline BRCA pathogenic variants (PVs). Limited data exist on the impact of different histologic BC subtypes in young patients with a germline BRCA PV.
Methods
In this multicenter retrospective cohort study, women aged ≤40 years with newly diagnosed early-stage BC and germline PVs in BRCA1/2 from 78 centres worldwide were included. Histology was assessed locally. Patients whose tumors had mixed histologies were excluded from the comparative analysis of ductal vs. lobular tumors. Kaplan-Meier method and Cox regression analysis were used to assess differences in disease-free survival (DFS) and overall survival (OS) according to different histologies.
Results
Of 4,628 included patients, 3,969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared to ductal histology tumors, lobular tumors were more often grade 1/2 (57.7% vs. 22.1%), stage III (29.6% vs. 18.5%), and luminal A-like (42.2% vs. 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors had more often mastectomy (68.9% vs. 58.3%), and received less often chemotherapy (83.7% vs. 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in either DFS (adjusted hazard ratio (HR) 1.01, 95%CI 0.74-1.37) or OS (HR 0.96, 95%CI 0.62-1.50) between patients with ductal and lobular tumors. No significant survival differences were observed between patients with lobular vs. ductal tumors according to BRCA gene affected (BRCA 1 vs. 2), BC subtype (luminal-like, HER2-positive, triple-negative) and body mass index (<25 vs. ≥25).
Conclusions
In this large global cohort of young BC patients with germline BRCA1/2 PVs, the incidence of pure lobular histology was low (3%) and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. While histologic subtype did not appear to impact prognosis, further research is warranted to determine the incremental benefits of newer therapeutic approaches (e.g., PARPi) on outcomes by subtype in this population.
Clinical trial identification
NCT03673306.
Legal entity responsible for the study
The BRCA BCY Collaboration.
Funding
Has not received any funding.
Disclosure
E. Agostinetto: Financial Interests, Personal, Invited Speaker: AstraZenece, Eli Lilly; Financial Interests, Personal, Writing Engagements: Sandoz; Financial Interests, Personal, Other, Travel grant: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Research Grant, Research grant to my Institution: Gilead. S. Linn: Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AstraZeneca, Cergentis, IBM; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Tesaro/GSK, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, Novartis; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Daiichi Sankyo Europe GmbH. K. Pogoda: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Gilead, Novartis, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Sandoz, AstraZeneca; Financial Interests, Personal, Full or part-time Employment, Assistant Professor: Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Financial Interests, Personal and Institutional, Other, SI: Novartis, Roche, Eli Lilly, AstraZeneca; Non-Financial Interests, Other, Breast Cancer Group - Steering Committee Member, Quality of Life Group: EORTC; Non-Financial Interests, Member: Polish Society of Clinical Oncology, Polish Society of Oncology. F. Derouane: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Congress and travel fees: Gilead. J. Bajpai: Financial Interests, Institutional, Invited Speaker, Institute financial interest for conducting the research study: Eli Lilly, Novartis, Roche, Paxman Coolers Ltd.; Financial Interests, Institutional, Invited Speaker, Institute financial interest for conducting the research study.(completed study): Samsung Bioepis co. Ltd.; Financial Interests, Institutional, Invited Speaker, Institutional financial interests for conducted research(completed study): Sun Pharma; Financial Interests, Institutional, Invited Speaker, Institute financial interest for conducting research study: MSD; Financial Interests, Institutional, Research Grant, Supporting with drugs for the research study: Intas Pharmaceuticals Ltd.; Non-Financial Interests, Advisory Role: Novartis; Non-Financial Interests, Leadership Role, Founder General Secretary: Immuno-Oncology Society of India (IOSI); Non-Financial Interests, Leadership Role, Executive Committee Member: Indian Society of Medical and Paediatric Oncology (ISMPO); Non-Financial Interests, Leadership Role, Founder Member and Joint Secretory: Teenage and Young Adult Cancer Foundation (TYAcan); Non-Financial Interests, Leadership Role, Managing Committee Member: Indian cooperative Oncology network (ICON); Non-Financial Interests, Leadership Role, Women for oncology -core committee member: ESMO; Non-Financial Interests, Leadership Role, Faculty-investigational immunotherapy: ESMO; Non-Financial Interests, Leadership Role, Global access and Impact Committee member: SITC. A.H. Partridge: Financial Interests, Royalties: Wolters Kluwer ; Financial Interests, Research Grant: Novartis. K. Phillips: Non-Financial Interests, Advisory Board, unpaid advisory role: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. A. Toss: Financial Interests, Personal, Other: Pfizer, Eli Lilly, Novartis, Gilead, Seagen, MSD, AstraZeneca, Daiichi Sankyo. C. Rousset-Jablonski: Financial Interests, Institutional, Advisory Role: Roche, Theramex, Gedeon Richter; Financial Interests, Institutional, Invited Speaker: Novartis, Organon, Theramex; Financial Interests, Institutional, Research Grant: Bayer Healthcare. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/Gne, Novartis, Seagen, MSD; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Other, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead Sciences; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, ASCENT 04: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: AstraZeneca; Financial Interests, Personal, Other, Travel grant: AstraZeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund; Non-Financial Interests, Leadership Role, President 2023-2026: Belgian Society of Medical Oncology (BSMO). E. Blondeaux: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Research Grant, research funding (to the institution): Gilead. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Invited Speaker, 2-year research grant paid to my Institution: Gilead. All other authors have declared no conflicts of interest.