HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma

Peter A. Learn, I. Tien Yeh, Michelle McNutt, Gary B. Chisholm, Bradley H Pollock, Dennis L. Rousseau, Frances E. Sharkey, Anatolio B. Cruz, Morton S. Kahlenberg

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2252-2260
Number of pages9
JournalCancer
Volume103
Issue number11
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

docetaxel
Breast Neoplasms
Neoplasms
Progesterone Receptors
Estrogen Receptors
Drug Therapy
Taxoids
Phase III Clinical Trials
Anthracyclines

Keywords

  • Breast carcinoma
  • HER-2/neu
  • Neoadjuvant chemotherapy
  • Taxanes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Learn, P. A., Yeh, I. T., McNutt, M., Chisholm, G. B., Pollock, B. H., Rousseau, D. L., ... Kahlenberg, M. S. (2005). HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma. Cancer, 103(11), 2252-2260. https://doi.org/10.1002/cncr.21037

HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma. / Learn, Peter A.; Yeh, I. Tien; McNutt, Michelle; Chisholm, Gary B.; Pollock, Bradley H; Rousseau, Dennis L.; Sharkey, Frances E.; Cruz, Anatolio B.; Kahlenberg, Morton S.

In: Cancer, Vol. 103, No. 11, 01.06.2005, p. 2252-2260.

Research output: Contribution to journalArticle

Learn, PA, Yeh, IT, McNutt, M, Chisholm, GB, Pollock, BH, Rousseau, DL, Sharkey, FE, Cruz, AB & Kahlenberg, MS 2005, 'HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma', Cancer, vol. 103, no. 11, pp. 2252-2260. https://doi.org/10.1002/cncr.21037
Learn, Peter A. ; Yeh, I. Tien ; McNutt, Michelle ; Chisholm, Gary B. ; Pollock, Bradley H ; Rousseau, Dennis L. ; Sharkey, Frances E. ; Cruz, Anatolio B. ; Kahlenberg, Morton S. / HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma. In: Cancer. 2005 ; Vol. 103, No. 11. pp. 2252-2260.
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title = "HER-2/neu expression as a predictor of response to neoadjuvant docetaxel in patients with operable breast carcinoma",
abstract = "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.",
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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, Bradley 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.

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