title: Use of statins and breast cancer: a meta-analysis of seven randomized clinical trials and nine observational studies.
abstract: OBJECTIVE
  A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature.
  
  
  METHODS
  A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed.
  
  
  RESULTS
  Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results.
  
  
  CONCLUSIONS
  Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Athens, 75 Mikras Asias Str, Athens 11527, Greece. sbonovas@med.uoa.gr
authors.forename: Stefanos
authors.initials: S
authors.lastname: Bonovas
authors.forename: Kalitsa
authors.initials: K
authors.lastname: Filioussi
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tsavaris
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Sitaras
mesh_terms: D001943:Breast Neoplasms / Q000517:prevention & control*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors