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  • Title: Oral contraceptive use and other risk factors in relation to HER-2/neu overexpression in breast cancer among young women.
    Author: Gammon MD, Hibshoosh H, Terry MB, Bose S, Schoenberg JB, Brinton LA, Bernstein JL, Thompson WD.
    Journal: Cancer Epidemiol Biomarkers Prev; 1999 May; 8(5):413-9. PubMed ID: 10350436.
    Abstract:
    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 (< or =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. This population-based study was undertaken to address the hypothesis that the incidence of breast tumor with a high HER-2/neu+ protein product was associated with oral contraceptive (OC) use and other risk factors compared with HER-2/neu- tumors. The study was conducted through the collection of archived paraffin-embedded tissue blocks, laboratory evaluation and combined laboratory results with risk factor information. About 159 of 371 (42.9%) in-situ and invasive breast cancer cases showed overexpression of HER-2/neu+ during immunohistochemistry of archived tissue. During the statistical analysis using a polytomous logistic regression, odds ratio (OR) was calculated and 95% confidence interval (CI) for HER-2/neu+ breast cancer and HER-2/neu- breast cancer compared with 401 controls regarding OC use and other risk factors. The OR (HER-2/neu+ vs. 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 OR, 1.29; 95% CI, 0.83-2.00). In early pill users, heterogeneity by HER-2/neu status was apparent (2.39; 95% CI, 1.08-5.30). A 5-fold increase in heterogeneity risk was noted among women with estrogen receptor (ER) negative tumors. In conclusion, 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 OR for positive tumors being twice that for negative tumors.
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