Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial.

Abstract

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.

• Authors: Judith Hugh, John Hanson, Maggie Chon U Cheang, Torsten O Nielsen, Charles M Perou, Charles Dumontet, John Reed, Maryla Krajewska, Isabelle Treilleux, Matthieu Rupin, Emmanuelle Magherini, John Mackey, Miguel Martin, Charles Vogel
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 8 Pg. 1168-76 (Mar 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19204205 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, Estrogen
• Taxoids
• Tamoxifen
• Docetaxel
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (classification, drug therapy, mortality, pathology)
• Docetaxel
• Female
• Humans
• Immunohistochemistry
• Lymphatic Metastasis
• Middle Aged
• Receptor, ErbB-2 (analysis)
• Receptors, Estrogen (analysis)
• Tamoxifen (therapeutic use)
• Taxoids (administration & dosage)