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In GeparSixto, 17% of triple-negative patients carried a germline BRCA1 or BRCA2 mutation; they responded well to chemotherapy whether or not carboplatin was added, while it was the non-carriers whose complete response rate rose from 36% to 55% with carboplatin.
Archived DNA from 291 of 315 TNBC patients in GeparSixto (NCT01426880) was analysed for germline mutations in BRCA1, BRCA2 and 16 other predisposition genes. Pathological complete response (ypT0/is ypN0) was 56.8% with carboplatin and 41.4% without (OR 1.87). Pathogenic BRCA1/2 germline mutations were present in 50 patients (17.2%). Without carboplatin, pCR was 66.7% in carriers versus 36.4% in non-carriers (OR 3.50); carboplatin did not raise the carriers' rate further (65.4%) but raised non-carriers' from 36.4% to 55% (OR 2.14), and non-carriers gained disease-free survival with carboplatin (85.3% versus 73.5%; HR 0.53).
Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.
Shares Carsten Denkert, Sibylle Loibl, German Breast Group (GBG), Pathologic complete response (pCR).
Shares Carsten Denkert, Sibylle Loibl, German Breast Group (GBG), Pathologic complete response (pCR).
Shares Carsten Denkert, Sibylle Loibl, German Breast Group (GBG), GeparSixto.
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA), BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA), BRCA1 / BRCA2 (HRD), Triple-negative breast cancer (TNBC).
Shares GeparSixto, Pathologic complete response (pCR), BRCA1 / BRCA2 (HRD), Early triple-negative breast cancer.
Shares Germline BRCA1/2 pathogenic variant (gBRCAm), Germline BRCA mutation (gBRCA), BRCA1 / BRCA2 (HRD), Carboplatin.
Shares Germline BRCA mutation (gBRCA), Pathologic complete response (pCR), BRCA1 / BRCA2 (HRD), Early triple-negative breast cancer.