Responsiveness of intrinsic subtypes to adjuvant anthracycline substitution in the NCIC.CTG MA.5 randomized trial.

摘要: Purpose: Recent studies suggest that intrinsic breast cancer subtypes may differ in their responsiveness to specific chemotherapy regimens. We examined this hypothesis on NCIC.CTG MA.5, a clinical trial randomizing premenopausal women with node-positive adjuvant CMF (cyclophosphamide-methotrexate-fluorouracil) versus CEF (cyclophosphamide-epirubicin-fluorouracil) chemotherapy. Experimental Design: Intrinsic subtype was determined for 476 tumors using the quantitative reverse transcriptase PCR PAM50 gene expression test. Luminal A, luminal B, HER2-enriched (HER2-E), and basal-like were correlated relapse-free survival (RFS) overall (OS), estimated Kaplan–Meier plots log-rank testing. Multivariable Cox regression analyses significance of interaction between treatment subtypes. Results: associated RFS ( P = 0.0005) OS 0.03 OS). Within clinically defined Her2 + tumors, 79% (72 91) classified as HER2-E by subset strongly better response (62% vs. 22%, 0.0006). There no significant difference benefit [ n 94; HR, 1.1; 95% confidence interval (CI), 0.6–2.1 1.3; CI, 0.7–2.5 OS]. Conclusion: predicted anthracycline sensitivity. The chemotherapy-sensitive showed added over CMF, suggesting nonanthracycline regimens be adequate although further investigation is required. Clin Cancer Res; 18(8); 2402–12. ©2012 AACR .