title: Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.
abstract: 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 and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 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 two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) 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, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites 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 estrogen metabolite 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 estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. heather.eliassen@channing.harvard.edu
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
authors.forename: Donna
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Larry K
authors.initials: LK
authors.lastname: Keefer
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Robert L
authors.initials: RL
authors.lastname: Barbieri
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002853:Chromatography, Liquid; D004964:Estriol / Q000097:blood / Q000737:chemistry / Q000652:urine; D004967:Estrogens / Q000097:blood / Q000378:metabolism* / Q000652:urine*; D004970:Estrone / Q000097:blood / Q000737:chemistry / Q000652:urine; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015394:Molecular Structure; D015999:Multivariate Analysis; D017697:Premenopause / Q000097:blood / Q000652:urine*; D018570:Risk Assessment / Q000706:statistics & numerical data; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D004967:Estrogens; D004970:Estrone; D004964:Estriol