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Oral Contraceptive Use and Other Risk Factors in Relation to HER-2/neu Overexpression in Breast Cancer Among Young Women¹

Columbia University, Joseph L. Mailman School of Public Health, Division of Epidemiology, New York, New York 10032 [M. D. G., M. B. T.]; Columbia College of Physicians and Surgeons, Department of Pathology, New York, New York 10032 [H. H., S. B.]; New Jersey State Department of Health and Senior Services, Applied Cancer Epidemiology Program, Trenton, New Jersey 08625 [J. B. S.]; National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, Maryland 20892 [L. A. B.]; Mt. Sinai Medical Center, Department of Community and Preventive Medicine, New York, New York 10029 [J. L. B.]; and University of Southern Maine, Department of Applied Medical Sciences, Portland, Maine 04103 [W. D. T.]

This study was undertaken to explore whether the incidence of breast tumors that overexpress HER-2/neu protein product (HER-2/neu+) is more strongly associated with oral contraceptives (OCs) and other factors than is the incidence of tumors that do not (HER-2/neu-). In a population-based sample of women <45 years, 42.9% (159 of 371) of in situ and invasive breast cancer cases were HER-2/neu+ as assessed by immunohistochemistry in archived tissue. Polytomous logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for HER-2/neu+ and HER-2/neu- breast cancer, as compared with 462 population-based controls, in relation to OCs and other factors. The ratio of the ORs (HER-2/neu+ versus HER-2/neu- tumors) was used as an indicator of heterogeneity in risk. There was little heterogeneity in risk for OC use of 6 months or more by HER-2/neu status (age-adjusted ratio of ORs, 1.29; 95% CI, 0.83–2.00). Among early pill users (18 years of age) heterogeneity was apparent (2.39; 95% CI, 1.08–5.30), which was attenuated in a multivariate model (1.99; 95% CI, 0.87–4.54); among cases with estrogen receptor-negative tumors, heterogeneity increased to 5-fold. For other risk factors, there was no marked heterogeneity between + and - tumors for HER-2/neu. In summary, the incidence of breast cancer among younger women in relation to OC use at an early age varied with HER-2/neu status, with the odds ratio for + tumors twice that for - tumors.

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