Abstract 2784: Urinary estrogen metabolites in the luteal phase and subsequent risk of breast cancer among premenopausal women

Higher levels of endogenous estrogen are associated with increased breast cancer risk in postmenopausal women. Data for premenopausal women are sparse, in part due to the complexity of measuring hormones that vary throughout the menstrual cycle. We previously reported increased breast cancer risks with higher plasma free and total estradiol in the follicular phase, but no statistically significant associations with plasma luteal phase estrogens. Individual patterns of estrogen metabolism may relate to breast cancer risk, though the hypothesized relationships have not been thoroughly explored, particularly among premenopausal women. Estrogen metabolism occurs via three main pathways, with hydroxylation of estrone and estradiol occurring at the C-2, C-4, and C-16 positions. We prospectively evaluated associations between 15 mid-luteal urinary estrogens and estrogen metabolites (EM) and breast cancer risk among premenopausal women in a case-control study nested within the Nurses9 Health Study II. From 1996 to 1999, urine samples were collected from 18,521 premenopausal women during the mid-luteal phase of their menstrual cycle. 251 cases of breast cancer were diagnosed among these women after urine collection and before June 1, 2005. These cases were matched to 500 controls. Urinary EM were measured using a liquid chromatography-tandem mass spectrometry method with high sensitivity, specificity, and precision. We used logistic regression models, controlling for breast cancer risk factors, to calculate relative risks (RRs) and 95% confidence intervals (CIs). Using both absolute (pmol/mg creatinine) and relative (% of total EM) levels, we assessed the associations with breast cancer risk of individual EM, as well as EM grouped according to chemical or metabolic characteristics. Overall, in preliminary analyses, we did not observe significant positive associations between any of the 15 EM and breast cancer risk, except with 17-epiestriol, a low concentration metabolite in the 16-hydroxylation pathway (absolute level top vs. bottom quartile RR=1.5, 95% CI (0.9-2.3), p-trend=0.05; relative level top vs. bottom quartile RR=1.7, 95% CI (1.1-2.8), p-trend=0.03). We observed inverse associations with absolute and relative measures of estrone and estradiol (e.g., absolute estrone top vs. bottom quartile RR=0.5, 95% CI (0.3-0.9), p-trend=0.005; absolute estradiol top vs. bottom quartile RR=0.6, 95% CI (0.3-0.9), p-trend=0.01). Ratios of grouped metabolites (e.g., 2-hydroxylation:16-hydroxylation pathways) were not significantly associated with risk. These data suggest that most mid-luteal urinary EM are not positively associated with breast cancer risk among premenopausal women. Our findings of inverse associations with urinary estrone and estradiol suggest that women with higher urinary excretion of parent estrogens may be at lower breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2784.