Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial - PubMed (original) (raw)

. 2009 Mar 10;27(8):1168-76.

doi: 10.1200/JCO.2008.18.1024. Epub 2009 Feb 9.

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

Affiliations

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

Judith Hugh et al. J Clin Oncol. 2009.

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.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Fig 1.

Disease-free and overall survival among patients according to biologic subtype. (A) Disease-free survival and (B) overall survival for patients stratified into triple-negative (estrogen receptor [ER] negative, progesterone receptor [PR] negative, HER2/neu [HER2] negative), HER2 (HER2-positive, ER-negative, PR-negative), luminal B (LB; ER-positive or PR-positive and either HER2-positive or Ki67high) and luminal A (LA; ER-positive or PR-positive and not HER2-positive or Ki67high) groups. Pairwise comparisons between subtypes were statistically significant (see text).

Fig 2.

Fig 2.

Disease-free survival (DFS) among patients treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or docetaxel, doxorubicin, and cyclophosphamide (TAC) according to biologic subtype. Disease-free survival is shown in patients classified as (A) triple negative, (B) HER2, (C) luminal B, or (D) luminal A treated with FAC or TAC. P values in each panel are logistic regression calculations based on 3-year DFS. ER, estrogen receptor; PR, progesterone receptor.

Fig 3.

Fig 3.

Forest plot of covariate adjusted hazard ratios (HR) for disease-free survival in patients in the luminal A and luminal B groups by treatment (hazard ratios and 95% CIs using fluorouracil, doxorubicin, and cyclophosphamide and no tamoxifen as baseline treatments). Values less than 1 show an advantage to docetaxel, doxorubicin, and cyclophosphamide (TAC) or tamoxifen.

Fig 4.

Fig 4.

Disease-free survival among estrogen receptor positive patients treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or docetaxel, doxorubicin, and cyclophosphamide (TAC) according to HER2 status and tamoxifen (Tamox) treatment. Disease-free survival for estrogen receptor (central lab)–positive patients, (A) positive or (C) negative for HER2, by treatment arm. (B, D) Subdivision of these patients by tamoxifen treatment. Log-rank P values are descriptive only.

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