HER2and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
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BACKGROUND: Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens. METHODS: In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 710 premenopausal women with node-positive breast cancer who had received either cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was evaluated with the use of fluorescence in situ hybridization, immunohistochemical analysis, and polymerase-chain-reaction analysis. RESULTS: Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02). CONCLUSIONS: Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy. (cancer.gov number, NCI-V90-0027.).
