title: Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action.
abstract: BACKGROUND
  Raloxifene is a selective estrogen-receptor modulator (SERM) indicated for the prevention and treatment of osteoporosis in postmenopausal women. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, an osteoporosis treatment trial, raloxifene therapy was associated with a reduced incidence of invasive, estrogen receptor (ER)-positive breast cancer compared with placebo (relative risk, 0.16; 95% CI, 0.09-0.30).
  
  
  OBJECTIVE
  This review summarizes available preclinical and clinical data pertaining to a potential role for raloxifene in the prevention of breast cancer, and examines the mechanisms of action by which raloxifene may exert an effect.
  
  
  METHODS
  Relevant articles were identified through a search of MEDLINE for English-language studies published between 1966 and January 2003. Search terms included raloxifene, keoxifene, tamoxifen, SERM, estrogen, estrogen receptor, breast, mammary, growth factors, and apoptosis. The reference lists of identified articles were reviewed for additional publications.
  
  
  RESULTS
  Both preclinical and clinical data suggest a role for raloxifene in the prevention of breast cancer. Like tamoxifen, raloxifene acts as an estrogen antagonist in breast tissue through competitive binding to the ER. Raloxifene may also inhibit breast tissue proliferation through mechanisms independent of the ER.
  
  
  CONCLUSIONS
  Given raloxifene's mechanism of action and the preclinical evidence for its role in breast cancer prevention, a clinically favorable effect seems feasible. Results of ongoing clinical studies will provide evidence to support or refute the clinical findings of MORE and thus raloxifene's role in the breast cancer prevention.
authors.affiliation: Dartmouth Medical School, Hanover, New Hampshire 03755, USA. michael.sporn@dartmouth.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
authors.forename: Sherie A
authors.initials: SA
authors.lastname: Dowsett
authors.forename: John
authors.initials: J
authors.lastname: Mershon
authors.forename: Henry U
authors.initials: HU
authors.lastname: Bryant
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000517:prevention & control*; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004965:Estrogen Antagonists; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride