Tumor BRCA1 Reversion Mutation Arising during Neoadjuvant Platinum-Based Chemotherapy in Triple-Negative Breast Cancer Is Associated with Therapy Resistance.

ABSTRACT: Purpose: In germline BRCA1 or BRCA2 (BRCA1/2) mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation is recognized as a mechanism of resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We evaluated this mechanism of resistance in newly diagnosed patients with BRCA1/2-mutant breast cancer with poor response to neoadjuvant platinum-based therapy.Experimental Design: PrECOG 0105 was a phase II neoadjuvant study of gemcitabine, carboplatin, and iniparib in patients with stage I-IIIA triple-negative or BRCA1/2 mutation-associated breast cancer (n = 80). All patients underwent comprehensive BRCA1/2 genotyping. For mutation carriers with moderate or extensive residual disease after

SUBMITTER: Afghahi A 

PROVIDER: S-EPMC5496787 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature