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

• Published in: Journal of clinical oncology Vol. 27; no. 8; pp. 1168 - 1176
• Main Authors: HUGH, Judith, HANSON, John, MAGHERINI, Emmanuelle, MACKEY, John, MARTIN, Miguel, VOGEL, Charles, CHEANG, Maggie Chon U, NIELSEN, Torsten O, PEROU, Charles M, DUMONTET, Charles, REED, John, KRAJEWSKA, Maryla, TREILLEUX, Isabelle, RUPIN, Matthieu
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.03.2009
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - classification; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Middle Aged; Original Reports; Receptor, ErbB-2 - analysis; Receptors, Estrogen - analysis; Tamoxifen - therapeutic use; Taxoids - administration & dosage; Tumors; Antineoplastic agent; Immunohistochemistry; Breast disease; Docetaxel; Definition; Breast cancer; Malignant tumor; Mammary gland diseases; Anatomic pathology; Cancerology; Taxane derivatives; Clinical trial; Antimitotic; Subtype; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.18.1024

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. 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. 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. 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.