Originally published as JCO Early Release 10.1200/JCO.2005.02.7045 on October 31 2005
Journal of Clinical Oncology, Vol 23, No 34 (December 1), 2005: pp. 8606-8612
© 2005 American Society of Clinical Oncology.
Use of Statins and Breast Cancer: A Meta-Analysis of Seven Randomized Clinical Trials and Nine Observational Studies
Stefanos Bonovas,
Kalitsa Filioussi,
Nikolaos Tsavaris,
Nikolaos M. Sitaras
From the Departments of Pharmacology and Pathophysiology, School of Medicine, University of Athens; and Department of Epidemiological Surveillance and Intervention, Hellenic Center for Infectious Disease Control, Athens, Greece
Address reprint requests to Stefanos Bonovas, MD, MSc, Department of Pharmacology, School of Medicine, University of Athens, 75 Mikras Asias Str, Athens 11527, Greece; e-mail: sbonovas{at}med.uoa.gr
PURPOSE: 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.
PATIENTS AND 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.
CONCLUSION: 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' disclosures of potential conflicts of interest are found at the end of this article.
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