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Clinical Cancer Research Vol. 11, 5678-5685, August 15, 2005
© 2005 American Association for Cancer Research

Human Cancer Biology

Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy

Roman Rouzier1,4, Charles M. Perou5, W. Fraser Symmans2, Nuhad Ibrahim1, Massimo Cristofanilli1, Keith Anderson3, Kenneth R. Hess3, James Stec6,7, Mark Ayers6, Peter Wagner1, Paolo Morandi1, Chang Fan5, Islam Rabiul1, Jeffrey S. Ross6, Gabriel N. Hortobagyi1 and Lajos Pusztai1

Authors' Affiliations: Departments of 1 Breast Medical Oncology, 2 Pathology, and 3 Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center, Houston, Texas; 4 Unité Propre de l'Enseignement Supérieur EA 3535, Institut Gustave Roussy, Villejuif, France; 5 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6 Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts; and 7 Albany Medical College, Albany, New York

Requests for reprints: Lajos Pusztai, Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Unit 424, 1515 Holcombe Boulevard, Houston, TX 77030-4009. Phone: 713-792-2817; Fax: 713-794-4385; E-mail: lpusztai{at}mdanderson.org.

Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy.

Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class.

Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor–negative subtypes.

Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.




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