Prospective neoadjuvant study of DNA-based biomarkers as predictors of carboplatin response in HER2-negative breast cancer

Although neoadjuvant carboplatin (Cb) improves outcomes in triple-negative breast cancer (TNBC), responses vary, and its role in aggressive hormone receptor-positive (HR+) remains uncertain. A prospective, randomized neoadjuvant study at Oslo University Hospital (Norway) evaluated DNA-based biomarkers to identify patients with early, high-risk HER2-negative breast cancer most likely to benefit from Cb. Patients (n=187) with cT2-4 HR+ BC or TNBC received 12 weekly doses of paclitaxel with or without Cb, followed by four cycles of epirubicin and cyclophosphamide. Among patients with TNBC (n=72), pathologic complete response (pCR) was obtained in 69% with Cb versus 43% with standard chemotherapy (p=0.036), whereas 74% and 65%, respectively, acquired either pCR or residual cancer burden class 1 (RCB 1; p=0.45). Cb significantly prolonged event-free survival (EFS; p=0.017). In patients with low genomic loss of heterozygosity (LOH) fraction, Cb improved EFS (p=0.007). A low genomic LOH fraction also indicated an unfavorable prognosis without Cb, confirmed in an independent cohort (n=67; p=0.02). Among patients with HR+ BC (n=115), pCR was 15% with Cb versus 11% with control (p=0.59), but the proportion achieving low RCB (pCR and RCB 1) increased from 16% without Cb to 35% with Cb (p=0.033). Among patients having HR+ BC tumors with homologous recombination deficiency, 5 of 8 attained pCR with Cb compared with 4 of 47 HRD-negative tumors. The authors conclude that this study indicates distinct predictive values of complex DNA-based biomarkers for breast cancer subtypes.