Abstract PS1-09-15: Prognostic Impact of BRCA Mutation Status on Outcomes with CDK4/6 Inhibitor Therapy in HR+/HER2- Metastatic Breast Cancer: A Real-World Cohort Study

Abstract Background: Germline BRCA mutations (gBRCA) are well-established predictors of therapeutic sensitivity in triple-negative breast cancer; however, their clinical implications in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC) treated with CDK4/6 inhibitors (CDK4/6i) remain poorly defined. We evaluated the association of gBRCA status with treatment patterns and clinical outcomes in a large real-world cohort of patients receiving CDK4/6i-based therapy. Methods: This retrospective cohort study included 3,000 patients with HR+/HER2- mBC treated with CDK4/6i between January 2015 to December 2024. Patients were stratified into three groups: gBRCA-mutated (n = 86), BRCA wild-type (n = 913), and those without germline testing (n = 2001). Demographics, tumor characteristics, treatment exposures, and outcomes were compared. Primary endpoints were progression-free survival (PFS) and overall survival (OS) from the initiation of CDK4/6i therapy. Kaplan-Meier analyses and univariate Cox proportional hazards models were used to assess survival outcomes by BRCA status. Results: Compared to BRCA wild-type patients, those with gBRCA mutations were younger at diagnosis (median age 44 vs. 52 years), more likely to have received platinum agents (24% vs. 9%) and PARP inhibitors (52% vs. 2%) in any treatment setting. No significant differences in ER or PR expression, HER2 IHC distribution, or site of progression were observed between groups. Median PFS was 11.3 months (95% CI: 7.4-15.6) in gBRCA patients, versus 20.7 months (95% CI: 17.6-23.1) in BRCA wild-type (WT) and 19.8 months (95% CI: 18.2-21.7) in untested patients (P