Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation

Background Efficacy of endocrine therapy in HR+/HER2− metastatic breast cancer could differ depending on the presence of BRCA1/2 germline mutation. Methods The ESME metastatic breast cancer platform (NCT03275311) is a French real world database. Multivariable models including a time-varying approach and landmark analyses assessed the association between time-dependent g BRCA status (categorised as g BRCA m, g BRCAwt (wild type), and untested), overall survival (OS), and first-line progression-free survival (PFS1). Results A total of 170 patients were g BRCA m carriers, 676 g BRC Awt, and 12,930 were untested at baseline. In the multivariable analysis, g BRCA m carriers overall had a lower OS compared to g BRCA wt (adjusted HR [95% CI] 1.26 [1.03–1.55]). g BRCA m patients treated with front-line endocrine therapy had lower adjusted OS (adjusted HR [95% CI] = 1.54 [1.03–2.32]) and PFS1 (adjusted HR [95% CI] 1.58 [1.17–2.12]) compared to g BRCA wt patients. However, for patients who received frontline chemotherapy, neither OS nor PFS1 differed between g BRCA m carriers and the other groups (HR versus g BRCA wt for OS: 1.12 [0.88–1.41], p = 0.350; PFS1: 1.09 [0.90–1.31], p = 0.379). Conclusion In this large cohort of HR+/HER2− MBC patients treated in a pre-CDK4/6 inhibitors era, g BRCA m status was associated with a lower OS and lower PFS following first-line endocrine therapy, but not following first-line chemotherapy.