title: Urinary estrogen metabolites and breast cancer: a combined analysis of individual level data.
abstract: BACKGROUND
  Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1), and their ratio (2:16α-OHE1) in relation to breast cancer risk.
  
  
  METHODS
  Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.
  
  
  RESULTS
  Higher premenopausal 2:16α-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16α-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003).
  
  
  CONCLUSIONS
  Premenopausal urinary 2:16α-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16α-OHE1 overall, although obesity may modify associations with 2-OHE1.
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. cher.dallal@nih.gov
authors.forename: Cher M
authors.initials: CM
authors.lastname: Dallal
authors.forename: Roslyn A
authors.initials: RA
authors.lastname: Stone
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Victor G
authors.initials: VG
authors.lastname: Vogel
authors.forename: Ian S
authors.initials: IS
authors.lastname: Fentiman
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Elaine N
authors.initials: EN
authors.lastname: Meilahn
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.forename: Anja
authors.initials: A
authors.lastname: Wellejus
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D001943:Breast Neoplasms / Q000652:urine*; D018270:Carcinoma, Ductal, Breast / Q000652:urine*; D016022:Case-Control Studies; D004964:Estriol / Q000652:urine; D004967:Estrogens / Q000652:urine*; D005260:Female; D006801:Humans; D016017:Odds Ratio; D017698:Postmenopause; D017697:Premenopause; D012306:Risk
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D004964:Estriol