ONCOmmunity

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

By: J-S Frenel, A Lusque, S Delaloge, J-M Ferrero, T Bachelot, I Desmoulins, C Levy, J-C Eymard, A Gonçalves, A Patsouris, M A Mouret Reynier, M J-C Thery, T Petit, L Cabel, L Uwer, M Debled, M Chevrot, A Mailliez, W Jacot, T de La Motte Rouge

Medical Oncology, ICO Institut de Cancerologie de l'Ouest René Gauducheau, Saint-Herblain, France. Jean-sebastien.frenel@ico.unicancer.fr.
2022-10-13; doi: 10.1038/s41416-023-02248-4

Abstract

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.