HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
Kathleen I. Pritchard, M.D., Lois E. Shepherd, M.D., Frances P. O'Malley, M.D., Irene L. Andrulis, Ph.D., Dongsheng Tu, Ph.D., Vivien H. Bramwell, M.B., B.S., Mark N. Levine, M.D., for the National Cancer Institute of Canada Clinical Trials Group
Background Amplification of the human epidermal growth factorreceptor type 2 (HER2, also called HER2/neu) gene and overexpressionof its product in breast-cancer cells may be associated withresponsiveness to anthracycline-containing chemotherapy regimens.
Methods In the randomized, controlled Mammary.5 trial, we studied639 formalin-fixed paraffin-embedded specimens obtained from710 premenopausal women with node-positive breast cancer whohad received either cyclophosphamide, epirubicin, and fluorouracil(CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF)as adjuvant chemotherapy. HER2 amplification or overexpressionwas evaluated with the use of fluorescence in situ hybridization,immunohistochemical analysis, and polymerase-chain-reactionanalysis.
Results Amplification of HER2 was associated with a poor prognosisregardless of the type of treatment. In patients whose tumorsshowed amplification of HER2, CEF was superior to CMF when assessedon the basis of relapse-free survival (hazard ratio, 0.52; 95percent confidence interval, 0.34 to 0.80; P=0.003) and overallsurvival (hazard ratio, 0.65; 95 percent confidence interval,0.42 to 1.02; P=0.06). For women whose tumors lacked amplificationof HER2, CEF did not improve relapse-free survival (hazard ratiofor relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18;P=0.49) or overall survival (hazard ratio for death, 1.06; 95percent confidence interval, 0.83 to 1.44; P=0.68). The adjustedhazard ratio for the interaction between treatment and HER2amplification was 1.96 for relapse-free survival (95 percentconfidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overallsurvival (95 percent confidence interval, 1.14 to 3.65; P=0.02).
Conclusions Amplification of HER2 in breast-cancer cells isassociated with clinical responsiveness to anthracycline-containingchemotherapy. (cancer.gov number, NCI-V90-0027.)
Source Information
From the Toronto Sunnybrook Regional Cancer Centre and the University of Toronto, Toronto (K.I.P.); Queen's University, Kingston, Ont. (L.E.S., D.T.); the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto (F.P.O., I.L.A.); the Department of Molecular and Medical Genetics, University of Toronto, and the Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto (I.L.A.); the Department of Oncology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alta. (V.H.B.); and the Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ont. (M.N.L.) — all in Canada.
Address reprint requests to Dr. Pritchard at Clinical Trials and Epidemiology, Toronto Sunnybrook Regional Cancer Centre, University of Toronto, 2075 Bayview Ave., Toronto, ON M4N 3M5, Canada, or at kathy.pritchard{at}sunnybrook.ca.
Anthracyclines in Early Breast Cancer
Wilson K. S., Pritchard K. I., Bramwell V. H., Levine M. N., the National Cancer Institute of Canada Clinical Trials Group , Piccart-Gebhart M. J.
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N Engl J Med 2006;
355:845-846, Aug 24, 2006.
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