Efficacy of front-line treatment for hormone receptor-positive HER2-negative metastatic breast cancer with germline BRCA1/2 mutation
Menée en France dans un contexte de vie réelle à partir de données portant sur des patientes atteintes d'un cancer du sein HR+ HER2+ de stade métastatique, cette étude de cohorte analyse l'effet, sur la survie globale et la survie sans progression, d'un traitement endocrinien de première ligne en fonction de la présence de mutations constitutionnelles BRCA1/2 (170 cas avec mutations, 676 cas sans mutation, 12 930 cas non testés)
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 gBRCA status (categorised as gBRCAm, gBRCAwt (wild type), and untested), overall survival (OS), and first-line progression-free survival (PFS1). Results: A total of 170 patients were gBRCAm carriers, 676 gBRCAwt, and 12,930 were untested at baseline. In the multivariable analysis, gBRCAm carriers overall had a lower OS compared to gBRCAwt (adjusted HR [95% CI] 1.26 [1.03–1.55]). gBRCAm 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 gBRCAwt patients. However, for patients who received frontline chemotherapy, neither OS nor PFS1 differed between gBRCAm carriers and the other groups (HR versus gBRCAwt 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, gBRCAm status was associated with a lower OS and lower PFS following first-line endocrine therapy, but not following first-line chemotherapy.