Abstract PD4-09: Impact of Duration of Adjuvant Endocrine Therapy on Clinical Outcomes in BRCA pathogenic variant Carriers with HR+/HER2- Early Breast Cancer

Abstract Background There is limited evidence on the effect of extended adjuvant endocrine therapy (ET) in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer (EBC) carrying germline BRCA1 and/or BRCA2 (gBRCA) pathogenic/likely pathogenic variants (PVs)compared to non-carriers. We investigated the association between extended ET (eET) versus standard-duration ET and clinical outcomes in gBRCA PV carriers with HR+/HER2- EBC. Methods This cohort study derived from an institutional database, including all consecutive patients with BC who underwent genetic counselling at the European Institute of Oncology (May 2002-Jan 2024). Eligible patients had stage I-III HR+/HER2- EBC diagnosed between Jan 2000 and Dec 2022, received adjuvant ET and had complete treatment and follow-up data available. eET was defined as therapy administered for more than 5 years. Primary endpoints were distant relapse-free interval (DRFI) and invasive disease-free survival (iDFS), as defined by STEEP 2.0 criteria. Survival analyses were conducted using univariate and multivariate Cox proportional-hazard models, stratified by year of diagnosis, use of (neo)adjuvant chemotherapy, nodal status, tumor size and grade, stage, ET duration and type BC surgery and BRCA PVs. Left-truncated models were used to account for the interval between BC diagnosis and genetic testing. Landmark analysis was performed to calculate the cumulative incidence of events over time. Results Among 1,225 eligible patients, the median duration of adjuvant ET was 60 months (IQR 49-74), with a median age of 41 years (IQR 36-47). The majority were premenopausal (79%, n=973), and 42% had stage I disease. Sixty percent received eET and 80% received LHRH agonists. Over half received tamoxifen, while 33% received aromatase inhibitors (AI), and 14% switched from tamoxifen to AI. Overall, 164 patients (13%) were gBRCA1/2 PV carriers, mostly gBRCA2 (76%). Carriers were younger than non-carriers (39 years, IQR 35-44 vs. 42 years, IQR 36-48), and more likely to have higher tumor stage (68% vs. 56% stage II/III) and grade (53% vs. 25% grade 3), to receive adjuvant chemotherapy and mastectomy, and to undergo BRCA testing earlier. The median duration of ET was similar in both groups, although a smaller proportion of BRCA PV carriers received eET compared to non-carriers (54% vs. 61%). At a median follow-up of 11.1 years (IQR [8.2-15.2]), extended ET was associated with significantly improved iDFS (adjusted HR [aHR] 0.31, 95% CI 0.26-0.39, p