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Originally published as JCO Early Release 10.1200/JCO.2008.18.1024 on February 9 2009 © 2009 American Society of Clinical Oncology. Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 TrialFrom the University of Alberta; Cross Cancer Institute, Edmonton, Alberta; Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, British Columbia, Canada; Lineberger Comprehensive Cancer Center and Departments of Genetics and Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; L'Institut National de la Santé et de la Recherche Médicale, U590; Hospices Civils de Lyon; Université Lyon; Centre Léon Bérard, Lyon; Cancer International Research Group; Sanofi-aventis, Paris, France; Burnham Institute for Medical Research, La Jolla, CA; Hospital Universitario San Carlos, Madrid, Spain; and Lynn Cancer Center, Boca Raton, FL. Corresponding author: Judith Hugh, MD, Department of Lab Medicine and Pathology, University of Alberta Hospital, 8440 112th St, Edmonton, Alberta, Canada T6G 2B7; e-mail: judith.hugh{at}capitalhealth.ca. Purpose To investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen. Methods Pathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]–negative, progesterone receptor [PR]–negative, HER2/neu [HER2]–negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67high), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67high), and assessed for prognostic significance and response to adjuvant chemotherapy. Results Patients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population. Conclusion A simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population. Supported by Grants No. P50-CA58223 and U01 CA114722-01 (to C.M.P.). Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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