HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer Journal Article

Authors: Berry, D. A.; Muss, H. B.; Thor, A. D.; Dressler, L.; Liu, E. T.; Broadwater, G.; Budman, D. R.; Henderson, I. C.; Barcos, M.; Hayes, D.; Norton, L.
Article Title: HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer
Abstract: Purpose: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized-physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. Patients and Methods: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. Results: HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. Conclusion: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does nat depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen. (C) 2000 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; adult; controlled study; human tissue; protein expression; middle aged; oncoprotein; human cell; major clinical study; clinical trial; doxorubicin; fluorouracil; dose response; drug efficacy; recurrence risk; lymph node metastasis; lymphatic metastasis; polymerase chain reaction; in situ hybridization, fluorescence; controlled clinical trial; breast cancer; gene expression; antineoplastic combined chemotherapy protocols; proportional hazards models; cyclophosphamide; drug resistance, neoplasm; breast neoplasms; protein p53; fluorescence in situ hybridization; diagnostic value; randomized controlled trials; tumor suppressor protein p53; tamoxifen; receptor, erbb-2; receptors, estrogen; antineoplastic agents, hormonal; postmenopause; oncogene neu; multicenter studies; humans; human; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 18
Issue: 20
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2000-10-20
Start Page: 3471
End Page: 3479
Language: English
PUBMED: 11032587
PROVIDER: scopus
Notes: Export Date: 18 November 2015 -- Source: Scopus