Statins to reduce breast cancer risk: A case control study in U.S. female veterans.

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: May 15, 2005

Presenter: R. Kochhar
Presenter's Affiliation: VA Medical Center, Shreveport, Louisiana
Type of Session: Scientific

Background

Statins (HMG CoA reducatse inhibitors) are a widely studied, effective class of medications used to lower cholesterol in an effort to reduce atherosclerosis and heart disease.
In certain animal models, statins have been shown to inhibit tumor growth.
The enzyme that statins inhibit (HMG CoA reductaste) has been demonstrated to be increased in tumor cells, and has also been show to be increased before DNA synthesis.
A theoretical mechanism for this inhibition is that certain cancer gene proteins require a lipid 'tail' to anchor them to tumor cells, and statins may prevent this from occurring.
HMG CoA reductase has also been demonstrated to be important in estrogen synthesis.
Little data exists on whether or not statins may prevent tumor growth in human beings, although some studies have reported increased risks of breast cancer with statin use.

Materials and Methods

A retrospective analysis of 40,421 patients from 10 VA medical centers was carried out to determine the effect that statin use has on the subsequent development of breast cancer.
The median age was 58 years (range 25-92).
Patients were classified as statin users if they had ever been prescribed a statin prior to the diagnosis of breast cancer.
Multiple logistic regression analysis was performed, with a 95% confidence interval employed.
The primary variables of interest were diagnosis of breast cancer and statin use.
Data was adjusted for smoking history, alcohol history, diagnosis of diabetes and age.

Results

Breast cancer was noted in 1.38% of women studied.
11.8% of patients examined were prescribed statins.
Statin users had a lower likelihood of developing breast cancer (odds ratio 0.49, p<0.0001)
When data was controlled for the covariates, they all remained highly significant: smoking OR 1.82 -> p<0.002, alcohol use OR 1.87 -> p<0.0001, older age OR 1.051 -> p<0.0001, and diagnosis of diabetes OR 1.83 -> p<0.0001.
Preliminary subgroup analyses demonstrate that the protective effect of stains increases with duration of statin use.

Author's Conclusions

Statins are associated with a 51% decreased risk of developing breast cancer when controlling for certain covariates.
This data needs to be evaluated with caution given the study design and limitations of the database.
Previously defined risk factors for the development of breast cancer were noted to be significant in this study, and this fact lends credibility to the database and findings.
A randomized, phase III trial to evaluate the protective effect of stains regarding the development of breast cancer is warranted.

Clinical/Scientific Implications

The authors present an enormous retrospective analysis where an association between statin use and breast cancer development is described. This large multi-institution database is a powerful tool for retrospective research. Because this is a retrospective study, it should be viewed as hypothesis generating, not hypothesis proving. The authors are correct in stating that limitations in the study design preclude definite conclusions about statins as a preventative measure for breast cancer. This analysis did not examine how the magnitude and duration of cholesterol lowering affected the risk of developing breast cancer. Nor did it make mention of the specific statins employed, or how long a patient took them. The analysis would be strengthened with these additional data. However, this study does raise a very interesting question. After further information is collected and analyzed, it may make sense to consider a randomized trial of a statin for breast cancer prevention in high risk patients.