title: Circulating estrogen metabolites and risk for breast cancer in premenopausal women.
abstract: BACKGROUND
  It has been proposed that a shift toward 2-hydroxyestrone from 16alpha-hydroxyestrone metabolic pathway may be inversely associated with breast cancer risk because 2-hydroxyestrone is thought to be less genotoxic and estrogenic than 16alpha-hydroxyestrone.
  
  
  METHODS
  We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone, 16alpha-hydroxyestrone, and the 2-hydroxyestrone:16alpha-hydroxyestrone ratio in a case-control study on premenopausal women nested within a prospective cohort the New York University Women's Health Study. The serum levels of 2-hydroxyestrone and 16alpha-hydroxyestrone were measured in 377 incident premenopausal breast cancer cases and 377 premenopausal controls, who were matched on age at enrollment, number and dates of blood donations, and day and phase of menstrual cycle.
  
  
  RESULTS
  Overall, no significant associations were observed between breast cancer risk and serum levels of 2-hydroxyestrone, 16alpha-hydroxyestrone, or their ratio. The 2-hydroxyestrone:16alpha-hydroxyestrone ratio was positively associated with risk for estrogen receptor-positive breast cancer in the analyses controlling for matching factors. However, the association was attenuated and not significant after adjustment for potential confounders (odds ratio for the highest versus the lowest quartile, 2.15; 95% CI, 0.88-5.27; P(trend) = 0.09).
  
  
  CONCLUSIONS
  The results of the current study do not support the hypothesis that a metabolic shift from 16alpha-hydroxyestrone toward 2-hydroxyestrone in premenopausal women is associated with reduced risk for breast cancer. The association between the 2-hydroxy:16alpha-hydroxyestrone ratio and estrogen receptor-positive breast cancer needs to be explored in future studies.
authors: Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors: Alan A
authors: AA
authors: Arslan
authors: Roy E
authors: RE
authors: Shore
authors: Yelena
authors: Y
authors: Afanasyeva
authors: Karen L
authors: KL
authors: Koenig
authors: Paolo
authors: P
authors: Toniolo
authors: Anne
authors: A
authors: Zeleniuch-Jacquotte
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000097:blood*; D008875:Middle Aged; D017697:Premenopause; D012307:Risk Factors
chemical_list: D004967:Estrogens; D006894:Hydroxyestrones