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Annals of Oncology Advance Access published online on May 21, 2007
Annals of Oncology, doi:10.1093/annonc/mdm209
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© 2007 European Society for Medical Oncology

Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: a biomarker study from two randomized trials

R Conforti1,{dagger}, T Boulet2,{dagger}, G Tomasic3,{dagger}, E Taranchon3, R Arriagada4, M Spielmann5, M Ducourtieux2, JC Soria5, T Tursz5, S Delaloge1,5, S Michiels2 and F Andre1,5,*

1 Translational research unit, Unite Propre de Recherche de l'enseignement supérieur, équipe d'accueil 03535
2 Biostatistics, and Epidemiology Unit
3 Department of Pathology
4 Department of Radiation Oncology
5 Department of Medicine, Institut Gustave Roussy, Villejuif, France

* Correspondence to: Dr F. Andre, Breast Cancer Unit, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. Tel: +33-1-42114371; Fax: +33-1-42115274; E-mail. fandre{at}igr.fr

Background: The purpose of this study was to determine the predictive value of breast cancer molecular subclassification regarding the benefit of adjuvant anthracycline-based chemotherapy.

Patients and methods: Tumor samples from 823 patients included in two randomized trials that compared an anthracycline-based chemotherapy with no treatment were used to construct a tissue array. Estrogen receptor (ER), Her2, epidermal growth factor receptor, cytokeratine 5/6 expressions were determined by immunohistochemistry (IHC). The potential predictive factors of treatment effect on disease-free survival (DFS) were assessed by interaction tests and multivariate analysis.

Results: Sixty-four (8%), 98 (12%), 109 (14%) and 527 (66%) patients presented a Her2+/ER–, basal-like, Her2–/ER–/nonbasal and luminal-like breast cancer. ER expression, when assessed by IHC, was an independent predictive factor for the benefit of chemotherapy on DFS (test for interaction, P = 0.0015). The molecular subclassification significantly predicted the efficacy of chemotherapy (test for interaction, P = 0.01), but had no significant added value (P = 0.32) as compared to the ER by treatment interaction. Adjuvant chemotherapy was associated with an adjusted hazard ratio for relapse or death of 0.42 [95% confidence interval (CI): 0.17–1.05], 0.54 (95% CI: 0.27–1.08), 0.35 (95% CI: 0.18–0.68), 1.07 (95% CI: 0.81–1.41) for patients with Her2+/ER–, basal-like, Her2–/ER–/nonbasal and luminal-like tumors, respectively.

Conclusion: The breast cancer molecular subclassification was predictive for chemotherapy efficacy in adjuvant setting, but did not provide significant additional information to ER.

adjuvant chemotherapy, basal like, breast cancer, estrogen receptor, molecular subclassification

{dagger} These authors contributed equally to this work.

Received for publication April 24, 2007. Accepted for publication April 25, 2007.


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