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HER-2/neu Overexpression and Response to Oophorectomy Plus Tamoxifen Adjuvant Therapy in Estrogen Receptor-Positive Premenopausal Women With Operable Breast Cancer

Richard R. Love, Nguyen Ba Duc, Thomas C. Havighurst, Syed K. Mohsin, Qian Zhang, David L. DeMets, D. Craig Allred

From the Departments of Medicine and Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI; Hospital K, Hanoi, Vietnam; People’s Hospital of Haimen City, Haimen, Jiangsu, China; and Department of Pathology, Baylor College of Medicine, Houston, TX.

Address reprint requests to Richard R. Love, 610 Walnut St. 256 WARF, Madison, WI 53726; email: rrlove{at}facstaff.wisc.edu.

Purpose: Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment. We studied 282 patients participating in a randomized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry.

Patients and Methods: Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used.

Results: HER-2/neu overexpression was a negative prognostic factor for overall survival. In univariate analyses, in HER-2/neu-positive patients, the hazard ratio (HR) for disease-free survival (DFS) with adjuvant endocrine therapy was 0.37 (95% confidence interval [CI], 0.26 to 0.89); for HER-2/neu-negative patients, the corresponding HR for DFS was 0.48 (95% CI, 0.31 to 0.71). The overall survival (OS) data were HR=0.26 (95% CI, 0.07 to 0.92) and HR=0.68 (95% CI, 0.32 to 1.42) for HER-2/neu-positive and HER-2/neu-negative patients, respectively. In multivariate models, the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS, respectively. Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment.

Conclusion: HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor–positive tumors.

Supported by grants from U.S. NIH CA 64339 and the International Breast Cancer Research Foundation, Madison, WI. Tamoxifen for this study was provided at cost by AstraZeneca Pharmaceuticals, Singapore.

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