title: The relation of urinary estrogen metabolites with mammographic densities in premenopausal women.
abstract: BACKGROUND
  Mammographic density is a strong predictor of breast cancer risk. The total amount and the metabolism of endogenous estrogens, e.g., the ratio of 2-hydroxyestrone (2-OHE(1)) and 16α-OHE(1) may influence breast cancer risk. This study examined the association of urinary estrogen metabolites with breast density in premenopausal women.
  
  
  METHODS
  Urine samples were collected at baseline and after 2 years, analyzed for 11 estrogen metabolites plus progesterone and testosterone by liquid chromatography mass spectrometry, and adjusted for creatinine levels. Mixed-effects regression was applied to examine the association of estrogens with breast density.
  
  
  RESULTS
  Total estrogen metabolites (181 ± 113 vs. 247 ± 165 pmol/mg creatinine, p=0.01) and the 2/16α-OH ratio (8.4 ± 10.4 vs. 13.0 ± 17.1, p=0.02) were lower in the 74 Asian than in the 114 non-Asian women. In adjusted models, positive associations of total estrogen metabolites (p=0.002) and the 2/16α-OHE(1) ratio (p=0.08) with percent density were detected in Asians only. In all women, mammographic density was positively associated with the 2-OH pathway (p=0.01), inversely related to the 16α-OH pathway (p=0.01), and not associated with the 4-OH pathway, testosterone, and progesterone. Results for the size of the dense area weakly reflected the findings for percent density, while associations with the non-dense area were in the opposite direction.
  
  
  CONCLUSIONS
  The findings that the 2-OH pathway is associated with higher and the 16α-OH pathway with lower breast density contradicts the hypothesized risk profile of these metabolites, but, if a relation between estrogen metabolites and breast cancer risk exists, it may be mediated through pathways other than mammographic density.
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA. gertraud@cc.hawaii.edu
authors.forename: Gertraud
authors.initials: G
authors.lastname: Maskarinec
authors.forename: Sreang
authors.initials: S
authors.lastname: Heak
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Laurie
authors.initials: L
authors.lastname: Custer
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Franke
mesh_terms: D000328:Adult; D044466:Asian People; D001940:Breast / Q000166:cytology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000652:urine; D002452:Cell Count; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000652:urine*; D008327:Mammography / Q000706:statistics & numerical data*; D008875:Middle Aged; D017697:Premenopause / Q000208:ethnology / Q000652:urine*; D011374:Progesterone / Q000652:urine; D018570:Risk Assessment; D013739:Testosterone / Q000652:urine
chemical_list: D004967:Estrogens; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D013739:Testosterone; D011374:Progesterone; C024980:2-hydroxyestrone