Statins and Breast Cancer: Yes, No, or Maybe

Abstract & Commentary

By William B. Ershler, MD, Editor

Synopsis: Statin drugs have been increasingly used for management of hypercholesterolemia. Preclinical studies indicated an antiproliferative effect in vitro and in rodent models of breast cancer. The current report is one of several that indicate a lack of evidence for reduction in breast cancer risk among statin users. However, the overall use of drugs in this class in the study cohort (7%) and the relatively short duration of use (approximately 4 years) suggest that the question is not completely resolved.

Source: Pocobelli G, et al. Cancer. 2008;112:27-33.

In vitro1 and animal studies2 have demonstrated an antiproliferative effect of statin drugs (3-hydroxyl-3 methylglutaryl coenzyme A reductase inhibitors) in certain breast cancer tumor models and these have engendered an intense interest to examine whether use of these drugs would be associated with reduced risk for breast cancer. To address this, Pocobelli and colleagues analyzed data from a population-based case-control study in which women 50 years of age or older with invasive breast cancer diagnosed between 1995-2001 were identified from population-based cancer registries in Wisconsin, Massachusetts, and New Hampshire. Controls were randomly selected from lists of licensed drivers and Medicare beneficiaries. Information on the use of statins and other breast cancer risk factors was ascertained from structured telephone interviews.

Overall, 7% of women ever used a statin and the mean cumulative duration of statin use was slightly greater for cases than controls (4.9 years vs 4.5 years, respectively). Analysis based upon the type of statin used, revealed that prior or current use of lipophilic statins as a group (simvastatin, lovastatin, and fluvastatin) and ever use of the hydrophilic statin pravastatin were also not associated with breast cancer risk. However, when examined singly, ever use of fluvastatin was associated with a decreased risk of breast cancer (odds ratio [OR], 0.5; 95% confidence interval, 0.3-0.8) but the reduction in risk was statistically significant only among users of less than 5 years (OR, 0.5; 95% CI, 0.3-0.9).

Commentary

Thus, the use of statins overall was not found to be associated with reduced breast cancer risk and this is consistent with a large literature, including a meta-analysis of 7 randomized trials and 9 observational studies examining breast cancer among statin users.3 The current multicenter population-based case-control study examined statins as a group, and specific drugs individually. However, the relatively short duration of treatment and low prevalence of statin use (7%) might suggest that, despite the negative result, the final answer might not be in. Also, the underlying condition for which the statin was prescribed (generally, hypercholesterolemia) might itself be a risk factor for breast cancer. An appropriate comparison, as noted by the authors, would be a comparison of statin users with users of other cholesterol-lowering agents over a long period of time. Unfortunately, the numbers were inadequate in the current study to result in reliable conclusions, and are unlikely in the near future outside of a randomized trial, because of the widespread use of drugs in this class at the current time. Alternatively, a placebo-controlled randomized study in women considered at high risk might be instructive.

References

1. Muck AO, et al. Int J Clin Pharmacol Ther. 2004;42(12):695-700.

2. Campbell MJ, et al. Cancer Res. 2006;66(17):8707-8714.

3. Bonovas S, et al. J Clin Oncol. 2005;23(34):8606-8612.