Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

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 Ki67(high)), and (4) luminal A ( ER-positive and/or PR-positive and not HER2-positive or Ki67(high)), 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.