Association Of Tumor Brca1 Reversion Mutation Arising During Neoadjuvant Platinum-Based Therapy In Breast Cancer (Bc) With Therapy Resistance.

1094 Background: In germline BRCA1 or BRCA2 mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation in these genes has been recognized as a mechanism of acquired resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We set out to evaluate this mechanism of resistance in newly diagnosed BRCA1/2-mutant BC patients (pts) with a poor response to platinum-based therapy. Methods: PrECOG 0105 was a single-arm phase II study in pts with clinical stage I-IIIA triple-negative (TN) or BRCA1/2 mutation-associated BC. Pts received neoadjuvant therapy with gemcitabine, carboplatin and iniparib every 21 days for 6 cycles (n = 80). The primary endpoint was pathologic complete response, defined as no invasive carcinoma in the breast and axilla. In addition to comprehensive germline BRCA1/2 testing, all pts underwent tumor BRCA1/2 genotyping using pre-treatment biopsies. For mutation carriers with unfavorable response (moderate or extensive residual disease at surgery), tumor BRC...