Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women

The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case-control study in 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort study, the Singapore Chinese Health Study, to evaluate the serum levels of estrogens and their receptor (ER alpha and ER beta)-mediated estrogenic activities in relation to breast cancer risk. Breast cancer cases had higher levels of estrogens and ER-mediated bioactivities in baseline serum than the controls. Compared with those in the lowest quartile, women in the highest quartile for estrone (E-1) or ER alpha-mediated bioactivity had increased breast cancer risk. After additional adjustment for ERb bioactivity, free estradiol, and E1 levels, serum ERa-mediated bioactivity remained associated with increased breast cancer risk. Compared with those in the lowest quartile, women in the highest quartile for ERa-mediated bioactivity had an odds ratio of 2.39 (95% CI=1.17-4.88; P for trend=0.016). Conversely, the positive association between E-1 and cancer risk became null after adjustment for ER alpha-mediated bioactivity, suggesting that the effect of E-1 could be mediated through ER alpha. Factor(s) contributing to increased ER alpha-mediated estrogenic bioactivity in serum and its role as a predictor for breast cancer risk need to be validated in future studies.