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Previous studies that have assessed breast cancer in relation to zinc, selenium, calcium, and iron have yielded inconsistent results but have not measured breast tissue levels. In a case-control study involving 252 matched pairs nested in a cohort of 9,315 women with benign breast disease, we investigated these associations by directly measuring elemental levels in breast tissue using X-ray fluorescence spectroscopy. Quintile analyses revealed positive associations of breast cancer, of borderline statistical significance, with zinc [highest versus lowest quintile: odds ratio (OR), 1.37; 95% confidence limit (95% CL), 0.91, 2.05; P(trend) = 0.04], iron (highest versus lowest quintile: OR, 1.58; 95% CL, 1.02, 2.44; P(trend) = 0.07), and calcium (highest versus lowest quintile: OR, 1.46; 95% CL, 0.98, 2.17; P(trend) = 0.14), but little association with selenium (highest versus lowest quintile: OR, 1.10; 95% CL, 0.72, 1.68; P(trend) = 0.76). The associations were weakened by mutual adjustment. Furthermore, after stratification by menopausal status, the positive association between iron and breast cancer was confined to postmenopausal women (highest versus lowest quintile: OR, 2.77; 95% CL, 1.25, 6.13; P(trend) = 0.008), whereas the associations for zinc, calcium, and selenium did not differ by menopausal stratum. In conclusion, our data raise the possibility that relatively high levels of zinc, iron, and calcium in benign breast tissue may be associated with a modest increase in risk of subsequent breast cancer.

Levels of Zinc, Selenium, Calcium, and Iron in Benign Breast Tissue and Risk of Subsequent Breast Cancer