Breast cancer molecular subtypes respond differently to preoperative chemotherapy

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  • Rouzier, Roman
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas; Unité Propre de l'Enseignement Supérieur EA 3535, Institut Gustave Roussy, Villejuif, France
  • Perou, Charles
  • Symmans, W. Fraser
    • Other Affiliation: Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Ibrahim, Nuhad
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Cristofanilli, Massimo
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Anderson, Keith
    • Other Affiliation: Department of Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Hess, Kenneth R.
    • Other Affiliation: Department of Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Stec, James
    • Other Affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts; Albany Medical College, Albany, New York
  • Ayers, Mark
    • Other Affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts
  • Wagner, Peter
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Morandi, Paolo
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Fan, Cheng
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Rabiul, Islam
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Ross, Jeffrey S.
    • Other Affiliation: Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts
  • Hortobagyi, Gabriel N.
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
  • Pusztai, Lajos
    • Other Affiliation: Department of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Abstract
  • 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 of82 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 ofpathologic 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 of6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31).Molecular class was not independent ofconventional cliniocopathologic predictors ofresponse such as estrogen receptor status and nuclear grade. None ofthe 61genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms ofchemotherapy sensitivity may vary between these two estrogen receptor ^ negative subtypes. Conclusions: The basal-like and erbB2+ subtypes ofbreast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normallike cancers.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Clinical Cancer Research
Journal volume
  • 11
Journal issue
  • 16
Page start
  • 5678
Page end
  • 5685
Language
  • English
Version
  • Postprint
ISSN
  • 1078-0432

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