Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites (EM) and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). In 1996-1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N=247) diagnosed between collection and June 2005 were matched to 2 controls each (N=485). Urinary EM were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR estrone=0.52, 95% CI=(0.30-0.88); estradiol=0.51, 95% CI=(0.30-0.86)). Generally inverse, though non-significant, patterns also were observed with 2- and 4-hydroxylation pathway EM. Inverse associations generally were not observed with 16-pathway EM and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR=1.74, 95% CI=(1.08-2.81), p-trend=0.01). In addition, there was a significant increased risk with higher 16-pathway/parent EM ratio (comparable RR=1.61, 95% CI=(0.99-2.62), p-trend=0.04). Other pathway ratios were not significantly associated with risk except parent EM/non-parent EM (comparable RR=0.58, 95% CI=(0.35-0.96), p-trend=0.03). These data suggest that most mid-luteal urinary EM concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent EM and the parent EM/non-parent EM ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.

PMID: 22144471 [PubMed - as supplied by publisher] Source: National Library of Medicine.