2974 - Prognostic Implications of Estrogen Exposure History for Breast Cancer Patients with BRCA1/2 Pathogenic Variants

Purpose/Objective(s): To determine if increased estrogen exposure history in women with BRCA 1/2 pathological variants (PVs) treated for Stage I-III breast cancer (BC) with adjuvant radiation differs from that of women with BRCA wild type (WT) genes, and to identify the effect of such differences on clinical outcomes.

Materials/Methods: We performed a retrospective analysis of data obtained from the Radiation Oncology Breast Database and the Risk Assessment Program registry of a single cancer center. Female patients were eligible for the study if they were treated for BC between 1995 and 2023 and their BRCA1/2 status (WT vs PV) was known. Characteristics including demographics, disease factors (clinical stage, hormone receptor status, histology, tumor grade), and treatment related outcomes were recorded. Estrogen exposure history elements analyzed included age of menarche (<12 vs =12 years), menopausal status (pre, peri, post), age of menopause (<45, 45-55, >55 years), parity, and age at first pregnancy (<30 vs =30 years). These characteristics were compared for the BRCA WT and PV groups using Chi-square or Fisher's exact test. Overall survival (OS) and progression-free survival (PFS) were determined by a 3-month landmark Kaplan-Meier methods and Cox proportional hazard models adjusting for BRCA, menopause status, stage, and age.

Results: A total of 998 patients were included in the study (938 BRCA WT, 60 BRCA1/2 PV). All patients received RT following surgery, 62% received chemotherapy (CHT), and 73% hormonal therapy (HT). Patients with BRCA PVs were younger at diagnosis than patients with BRCA WT (median age 46 vs 53 years, p<0.001), and were more likely to have triple-negative BC (40% vs. 13%, p<0.001) and high-grade tumors (68% vs. 41%, p<0.001). Clinical stage between the PV and WT cohorts were similar, but PVs more often received mastectomy (p<0.001), CHT (p<0.001), and HT (p=0.001). Pre-menopausal status was more common in patients in the BRCA PV groups (p=0.048), but no difference in age of menarche, age of menopause, parity, and age of first pregnancy was detected. Neither OS nor PFS differed between BRCA PVs and BRCA WT in the unadjusted and the adjusted models. Increased estrogen exposure risk factors (early menarche, late menopause, nulliparity, age of first birth =30 years) did not significantly impact OS or PFS for patients with BRCA PVs.

Conclusion: Women with BRCA1/2 PVs were found to be more often pre-menopausal than patients with BRCA WT, but OS and PFS for the two groups did not differ. Larger studies are warranted to pursue the possible prognostic implications of increased estrogen exposure history in BRCA1/2 PV patients.