160P Characteristics and outcomes of young breast cancer patients harboring BRCA pathogenic variants according to histologic subtype

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. 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. 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). 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.