Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness
Otto Metzger, Katharine A. Collier, Sarah Asad, Peter Ansell, Mark A. Watson, Junu Bae, Mathew Cherian, Joyce O’Shaughnessy, Michael Untch, Hope S. Rugo, Jens Huober, Mehra Golshan, William M. Sikov, Gϋnter von Minckwitz, Priya Rastogi, Lang Li, Lijun Cheng, David Maag, Norman Wolmark, Carsten Denkert, W. Fraser Symmans, Charles E. Geyer, Sibylle Loibl, Daniel G. Stover
Abstract
In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.