Germline mutation status and therapy response in high-risk early breast cancer: Results of the GeparOcto study (NCT02125344).

Abstract

573 Background: GeparOcto compared the efficacy of two neoadjuvant treatment (NAT) regimens in high-risk early breast cancer (BC): Sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carboplatin (PMCb) in triple-negative BC (TNBC). There was no difference in pathologic complete response (pCR) rates (Schneeweiss et al. Eur J Cancer 2019). Here, we stratified pCR rates according to germline mutation status. Methods: Germline (g) mutation analysis of BRCA1/2 and 16 further BC predisposition genes in 914 patients (pts) enrolled (393 pts with TNBC, iddEPC n = 194, PMCb n = 199; 156 pts with HER2-/HR+ BC, iddEPC n = 75, PM n = 81; and 365 pts with HER2+ BC, iddEPC n = 182, PM n = 183). Results: The gBRCA1/2 mutation prevalence was 17.6% in TNBC, 14.1% in HER2-/HR+ BC and 1.4% in HER2+ BC. Overall, pts with gBRCA1/2 mutations achieved higher pCR rates than gBRCA1/2 wildtype pts (60.4% vs 46.7%, OR 1.74, P = 0.012), with more pronounced effects in the PM(Cb) arm (68.1% vs 45.7%, OR 2.53, P = 0.005). Among gBRCA1/2 wildtype pts, 76 carried mutations in non- BRCA1/2 predisposition genes. pCR rates were similar to those observed in pts without any mutation. Conclusions: Pts with gBRCA1/2 mutations benefitted most from NAT with highest pCR rates achieved in the gBRCA1/2 TNBC / PMCb group. The role of Cb for NAT of gBRCA1/2 TNBC should be further explored. Clinical trial information: NCT02125344. [Table: see text]