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

• Published in: Cancer Vol. 103; no. 11; pp. 2252 - 2260
• Main Authors: Learn, Peter A., Yeh, I‐Tien, McNutt, Michelle, Chisholm, Gary B., Pollock, Brad H., Rousseau, Dennis L., Sharkey, Frances E., Cruz, Anatolio B., Kahlenberg, Morton S.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2005; Wiley-Liss
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; breast carcinoma; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Female; Gynecology. Andrology. Obstetrics; HER‐2/neu; Humans; Ki-67 Antigen - metabolism; Mammary gland diseases; Medical sciences; Middle Aged; neoadjuvant chemotherapy; Neoadjuvant Therapy; Neoplasm Invasiveness - pathology; Neoplasm Staging; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Survival Rate; taxanes; Taxoids - administration & dosage; Tumor Suppressor Protein p53 - metabolism; Tumors; Antineoplastic agent; Human; Docetaxel; taxanes; erbB2 Gene; Patient; Malignant tumor; Neoadjuvant treatment; Mammary gland diseases; Breast carcinoma; neoadjuvant chemotherapy; Cancerology; Taxane derivatives; C-Onc gene; HER-2/neu; Predictive factor; Antimitotic; Protooncogene
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21037

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. Cancer 2005. © 2005 American Cancer Society.
Among multiple prognostic factors that were evaluated, HER‐2/neu was identified as a potential predictive marker in neoadjuvant treatment with docetaxel. Whereas patients with HER‐2/neu‐positive tumors responded well to standard anthracycline‐based therapy either with or without the addition of docetaxel, patients with HER‐2/neu‐negative tumors demonstrated marked improvements in clinical response with the addition of docetaxel.