TY - JOUR
T1 - Breast cancer molecular subtypes respond differently to preoperative chemotherapy
AU - Rouzier, Roman
AU - Perou, Charles M.
AU - Symmans, W. Fraser
AU - Ibrahim, Nuhad
AU - Cristofanilli, Massimo
AU - Anderson, Keith
AU - Hess, Kenneth R.
AU - Stec, James
AU - Ayers, Mark
AU - Wagner, Peter
AU - Morandi, Paolo
AU - Fan, Chang
AU - Rabiul, Islam
AU - Ross, Jeffrey S.
AU - Hortobagyi, Gabriel N.
AU - Pusztai, Lajos
PY - 2005/8/15
Y1 - 2005/8/15
N2 - 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.
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.
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U2 - 10.1158/1078-0432.CCR-04-2421
DO - 10.1158/1078-0432.CCR-04-2421
M3 - Article
C2 - 16115903
AN - SCOPUS:23844549918
SN - 1078-0432
VL - 11
SP - 5678
EP - 5685
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -