Estrogen metabolites may play an important role in breast carcinogenesis. Animal and in vitro studies suggest differing biological effects of the 2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (16α-OHE1) metabolites, lending support to the use of 2:16α-OHE1 as a measure of estrogen balance. Although previous studies have evaluated the association between these specific metabolites and breast cancer among pre- and postmenopausal women, the results have been inconclusive. The sample size of individual studies is often small and lacks the statistical power to draw conclusions or to adequately assess the relationships within subgroups. Furthermore, the relationship between various lifestyle factors and personal characteristics and estrogen metabolites remains unclear. We evaluated the association between the 2-OHE1, 16α-OHE1 and 2:16α-OHE1 metabolites and breast cancer among premenopausal (183 cases/548 controls) and postmenopausal (319 cases/647 controls) women using a combined analysis of individual level data from previously published research studies. In separate study adjusted conditional logistic regression models matched on 5-year age groups, higher levels of 2:16α-OHE1 were not associated with breast cancer among pre- or postmenopausal women [Premenopausal: OR≥2.67 vs. <1.76=0.81 (95% CI: 0.49, 1.32); Postmenopausal: OR≥2.46 vs. <1.53=0.87 (95% CI: 0.58, 1.29)]. Using multivariable regression analyses adjusted for study, we evaluated various predictors of estrogen metabolites among the control populations of the participating studies (544 premenopausal/720 postmenopausal). Among premenopausal women, BMI was negatively associated with 2-OHE1 and 2:16α-OHE1 (p < 0.05). Analyses among postmenopausal women revealed significant associations (p<0.05) between age, age at menopausal status, and history of benign breast disease. In summary, this combined analysis does not support an association between urinary estrogen metabolites and breast cancer among pre- or post menopausal women. However, our results do suggest potential differences in factors related to estrogen metabolite levels among pre- and postmenopausal women. Enhancing our knowledge of estrogen metabolites among breast cancer patients and among healthy populations of women is a significant contribution to public health. By improving our understanding of estrogen metabolites we may be able to identify women at higher risk of breast cancer as well as increase our understanding of breast cancer etiology
