TY - JOUR
T1 - HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma
AU - Learn, Peter A.
AU - Yeh, I. Tien
AU - McNutt, Michelle
AU - Chisholm, Gary B.
AU - Pollock, Brad H.
AU - Rousseau, Dennis L.
AU - Sharkey, Frances E.
AU - Cruz, Anatolio B.
AU - Kahlenberg, Morton S.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - BACKGROUND. The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS. The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a ≥ 50% regression in clinical tumor size prior to surgery. RESULTS. In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS. HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.
AB - BACKGROUND. The use of biologic markers to predict response to neoadjuvant chemotherapy may permit tailoring regimens to achieve maximal tumor response. Taxanes have demonstrated excellent activity in breast carcinoma; however, tumor-specific factors that predict clinical response have not been characterized thoroughly. METHODS. The authors performed a historic review evaluating the association of tumor prognostic factors and response to neoadjuvant cyclophosphamide and doxorubicin (AC) with or without docetaxel (D) (AC vs. AC+D) in 121 women who previously were enrolled in a Phase III, randomized, clinical trial. Using pretreatment biopsy materials, immunohistochemical studies were performed for estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53, and Ki-67. Outcome variables were pathologic complete response (pCR) and positive clinical response (cPOS), which was defined as a ≥ 50% regression in clinical tumor size prior to surgery. RESULTS. In a multivariate analysis that controlled for tumor size and lymph node status, improved cPOS rates were observed with the addition of docetaxel in women with HER-2/neu-negative tumors (81% vs. 51%; P < 0.05), yielding an adjusted odds ratio of 3.5 (95% confidence interval, 1.2-13.0) in favor of docetaxel. Women who had HER-2/neu-negative tumors appeared to have a lower response rate with AC alone compared with women who had HER-2/neu-positive tumors (51% vs. 75%; P = 0.06), but response rates were matched when docetaxel was added (81% vs. 78%; P = 0.99). ER, PR, p53, and Ki-67 results were not associated significantly with response rates. CONCLUSIONS. HER-2/neu status may predict improved clinical response rates from the addition of docetaxel to anthracycline-based neoadjuvant chemotherapy. Docetaxel may "rescue" the response in women who have HER-2/neu-negative tumors to match that observed in women who have HER-2/neu-positive tumors treated with AC alone.
KW - Breast carcinoma
KW - HER-2/neu
KW - Neoadjuvant chemotherapy
KW - Taxanes
UR - http://www.scopus.com/inward/record.url?scp=18844445591&partnerID=8YFLogxK
U2 - 10.1002/cncr.21037
DO - 10.1002/cncr.21037
M3 - Article
C2 - 15834928
AN - SCOPUS:18844445591
SN - 0008-543X
VL - 103
SP - 2252
EP - 2260
JO - Cancer
JF - Cancer
IS - 11
ER -