A Prospective Study of Estradiol and Breast Cancer in Japanese Women

Few studies have prospectively examined endogenous hormone levels as risk factors for breast cancer. The present study compares prediagnostic hormone levels using stored serum from breast cancer cases and controls selected from the Life Span Study population of the Radiation Effects Research Foundation in Hiroshima and Nagasaki, Japan. Stored serum samples collected in 1968–1970 were assayed for 72 women subsequently diagnosed with breast cancer and 150 control subjects in 72 case-control sets matched on age, date of blood collection, exposure, radiation dose, and city. Serum levels were determined for sex hormone binding globulin, total estradiol (E 2 ), bioavailable E 2 , dehydroepiandrosterone sulfate, and prolactin. Matched case-control comparisons of hormone levels were carried out by conditional logistic regression and were adjusted for menopausal status at the time of blood drawing. The odds ratio per unit log change in bioavailable E 2 was 2.2 [95% confidence interval (CI), 1.02–5.3] for all subjects, and 2.3 (95% CI, 0.55–6.8) and 2.1 (95% CI, 0.55–9.7), respectively, based only on premenopausal or postmenopausal serum. The estimated odds ratios in each quintile of bioavailable E 2 level, using the lowest quintile as referent, were 1.00, 1.89, 1.43, 3.45, and 3.37 ( P for trend = 0.035). For sex hormone binding globulin, the overall odds ratio was 0.58 (95% CI, 0.14–2.26), and 1.00 (95% CI, 0.19–5.45) and 0.21 (95% CI, 0.02–1.88) based on premenopausal and postmenopausal serum, respectively. This study offers further prospective support for the hypothesis that a high level of biologically available E 2 is a risk factor for the subsequent development of breast cancer.