Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy.

Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. A nested case-control study was conducted within the prospective Danish population-based 'Diet, Cancer, and Health' cohort. During follow-up, 348 eligible cases were identified among 20,861 postmenopausal women and matched to 348 controls. Baseline serum samples were analyzed for estradiol, bioavailable estradiol, estrone, estrone sulfate, and SHBG. Conditional logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders. Modest direct associations were identified between estrogen levels and breast cancer incidence among both never and baseline HRT users. Estrone and estrone sulfate were more consistently associated among both groups than estradiol. No association was found with SHBG. Despite different hormonal profiles, higher serum estrogen levels were associated with a higher risk of breast cancer among both never and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.