A Phase Ii Clinical Trial To Analyze Olaparib Response In Patients With Brca1 And/Or Brca2 Promoter Methylation With Advanced Breast Cancer (Geicam/2015-06 Cometa-Breast Study).

TPS1114Background: Identification of targeted therapies for advanced triple negative breast cancer (TNBC) remains as an important clinical challenge. TNBC frequently shows BRCA dysfunction and 80% of germline BRCA1 mutation (gBRCAm) carriers with BC diagnosis are TNBC patients (pts). In addition to germline mutations, epigenetic silencing by aberrant methylation of BRCA1/2 promoters can be responsible for a dysfunctional BRCA protein. Methylation of BRCA1 promoter occurs in 15-57% of TNBCs. Interestingly, BRCA1-methylated sporadic breast tumors display pathologic features and gene expression profiles similar to those of gBRCAm carriers, a phenotype called “BRCAness”. Olaparib (O) is an oral poly (ADP-ribose) polymerase (PARP) inhibitor approved by the FDA for treatment of gBRCA-mutated HER2-negative metastatic BC. Tutt et al. have shown antitumor activity in gBRCA-mutated advanced TNBC (54% Objective Response Rate [ORR]). We report an ongoing phase II clinical trial to analyze the O efficacy in advanced T...