Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness

Author:

Metzger-Filho Otto,Collier KatharineORCID,Asad Sarah,Ansell Peter J.,Watson Mark,Bae Junu,Cherian Mathew,O’Shaughnessy Joyce,Untch Michael,Rugo Hope S.,Huober Jens B.,Golshan Mehra,Sikov William M.ORCID,von Minckwitz Gunter,Rastogi Priya,Li Lang,Cheng Lijun,Maag David,Wolmark Norman,Denkert CarstenORCID,Symmans W. FraserORCID,Geyer Charles E.ORCID,Loibl Sibylle,Stover Daniel G.ORCID

Abstract

AbstractIn 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.

Funder

Alliance Foundation [to D.G.S.] and Breast Cancer Research Foundation [to D.G.S.]

Conquer Cancer Foundation

Publisher

Springer Science and Business Media LLC

Subject

Pharmacology (medical),Radiology, Nuclear Medicine and imaging,Oncology

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