RT Journal Article
SR Electronic
T1 Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5678
OP 5685
DO 10.1158/1078-0432.CCR-04-2421
VO 11
IS 16
A1 Rouzier, Roman
A1 Perou, Charles M.
A1 Symmans, W. Fraser
A1 Ibrahim, Nuhad
A1 Cristofanilli, Massimo
A1 Anderson, Keith
A1 Hess, Kenneth R.
A1 Stec, James
A1 Ayers, Mark
A1 Wagner, Peter
A1 Morandi, Paolo
A1 Fan, Chang
A1 Rabiul, Islam
A1 Ross, Jeffrey S.
A1 Hortobagyi, Gabriel N.
A1 Pusztai, Lajos
YR 2005
UL http://clincancerres.aacrjournals.org/content/11/16/5678.abstract
AB 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.