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.
Highlights
In localized triple-negative breast cancer (TNBC), neoadjuvant chemotherapy (NAC) allows for assessment of pathologic response to chemotherapy
Expanding on I-SPY2, BrighTNess was a phase III, multicenter, international, randomized, double-blind, placebo-controlled clinical trial, which enrolled 634 patients with stage II/III TNBC 2:1:1 to NAC with: (A) paclitaxel plus carboplatin plus veliparib followed by doxorubicin plus cyclophosphamide (TCV-AC), (B) paclitaxel plus carboplatin followed by doxorubicin plus cyclophosphamide (TCAC), or (C) paclitaxel followed by doxorubicin plus cyclophosphamide (T-AC)
Similar to the overall BrighTNess analysis the entire cohort of mutated and non-mutated patients had higher Pathologic complete response (pCR) rates with the addition of carboplatin with or without veliparib compared to T-AC alone (Table 3)
Summary
In localized triple-negative breast cancer (TNBC), neoadjuvant chemotherapy (NAC) allows for assessment of pathologic response to chemotherapy. There was a trend among patients with germline BRCA mutations toward higher pCR rates compared to. Exploratory gene expression immune analyses suggested that tumors with higher inferred CD8+ T-cell infiltration may receive greater benefit with the addition of carboplatin[11]. Based on these data, we hypothesized that patients with BRCA mutated TNBC in the BrighTNess trial may benefit differentially from the addition of carboplatin or veliparib to NAC and may have. We analyzed the association of pCR rate with treatment arm in a matched cohort study of patients with germline BRCA1/2 (gBRCA) mutations compared to non-gBRCA controls.
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