title: Overview of the main outcomes in breast-cancer prevention trials.
abstract: BACKGROUND
  Early findings on the use of tamoxifen or raloxifene as prophylaxis against breast cancer have been mixed; we update available data and overview the combined results.
  
  
  METHODS
  All five randomised prevention trials comparing tamoxifen or raloxifene with placebo were included. Relevant data on contralateral breast tumours and side-effects were included from an overview of adjuvant trials of tamoxifen versus control.
  
  
  RESULTS
  The tamoxifen prevention trials showed a 38% (95% CI 28-46; p<0.0001) reduction in breast-cancer incidence. There was no effect for breast cancers negative for oestrogen receptor (ER; hazard ratio 1.22 [0.89-1.67]; p=0.21), but ER-positive cancers were decreased by 48% (36-58; p<0.0001) in the tamoxifen prevention trials. Age had no apparent effect. Rates of endometrial cancer were increased in all tamoxifen prevention trials (consensus relative risk 2.4 [1.5-4.0]; p=0.0005) and the adjuvant trials (relative risk 3.4 [1.8-6.4]; p=0.0002); no increase has been seen so far with raloxifene. Venous thromboembolic events were increased in all tamoxifen studies (relative risk 1.9 [1.4-2.6] in the prevention trials; p<0.0001) and with raloxifene. Overall, there was no effect on non-breast-cancer mortality; the only cause showing a mortality increase was pulmonary embolism (six vs two).
  
  
  CONCLUSIONS
  The evidence now clearly shows that tamoxifen can reduce the risk of ER-positive breast cancer. New approaches are needed to prevent ER-negative breast cancer and to reduce the side-effects of tamoxifen. Newer agents such as raloxifene and the aromatase inhibitors need to be evaluated. Although tamoxifen cannot yet be recommended as a preventive agent (except possibly in women at very high risk with a low risk of side-effects), continued follow-up of the current trials is essential for identification of a subgroup of high-risk, healthy women for whom the risk-benefit ratio is sufficiently positive.
authors.affiliation: Cancer Research UK, London, UK. jack.cuzick@cancer.org.uk
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.forename: U
authors.initials: U
authors.lastname: Veronesi
authors.forename: J
authors.initials: J
authors.lastname: Forbes
authors.forename: R
authors.initials: R
authors.lastname: Edwards
authors.forename: S
authors.initials: S
authors.lastname: Ashley
authors.forename: P
authors.initials: P
authors.lastname: Boyle
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D002423:Cause of Death; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride