DNA Biomarkers May Identify Carboplatin Benefit in High-Risk HER2-Negative Breast Cancer

A prospective randomized study assessed DNA-based biomarkers of carboplatin benefit in 187 patients with early, high-risk, HER2-negative cT2–4 breast cancer. Patients received 12 weekly paclitaxel treatments with or without carboplatin, followed by four cycles of epirubicin and cyclophosphamide. Pretreatment whole-exome sequencing assessed the complex arm-wise aberration index, loss of heterozygosity (LOH) fraction and homologous recombination deficiency (HRD). Outcomes included pathologic complete response (pCR), residual cancer burden and event-free survival (EFS).

Among patients with triple-negative breast cancer, pCR occurred in 69% (24/35) receiving carboplatin versus 43% (16/37) receiving control treatment (P=0.036). The combined pCR or residual cancer burden class 1 rate was 74% versus 65% (P=0.45). Carboplatin prolonged EFS (P=0.017), with an EFS benefit also observed in the low-LOH subgroup (P=0.007). Low LOH was associated with unfavorable prognosis without carboplatin, a finding confirmed in an independent cohort of 67 patients.

In hormone receptor–positive disease, pCR rates were 15% versus 11% (P=0.59), but combined pCR or class 1 residual burden increased from 16% to 35% (P=0.033). Among carboplatin-treated patients, 5/8 with HRD-positive tumors achieved pCR versus 4/47 with HRD-negative tumors (P=0.002).

These findings suggest subtype-specific biomarker associations, but do not establish routine biomarker-guided carboplatin selection. The abstract provides no EFS effect sizes, follow-up duration, safety results or biomarker-by-treatment interaction tests; the HRD-positive subgroup was small.