Estrogen receptor-negative breast cancer is less likely to arise among lipophilic statin users

Background: Preclinical studies have shown the anticancer potential of HMG-CoA reductase enzyme inhibitors (statins), whereas epidemiologic studies remain controversial. Because lipophilic statins show preclinical anticancer activity against hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)]-negative breast cancer models, we explored the hormone receptor phenotype of breast cancers that arise in statin users. Methods: We did a retrospective cohort analysis via electronic pharmacy records from the Kaiser Permanente Northern California Cancer Registry on 2,141 female patients listed in 2003 as incident cases of breast malignancy. Measures included tumor grade, stage, and receptor phenotype in statin users versus nonusers and controlled for hormone replacement therapy and race. Results: 387 of the 2,141 breast cancer patients used lipophilic statins [lovastatin (85%), simvastatin, and atorvastatin]. Fifty-one women developed ER/PR-negative tumors. The age-adjusted odds ratio (OR) of developing an ER/PR negative tumor was 0.63 (95% confidence interval, 0.43-0.92; P = 0.02) for statin use >= 1 year before breast cancer diagnosis compared with statin use < 1 year (including nonuse). Breast cancers in patients with >= 1 year of statin use were more likely to be low grade (OR, 1.44) and less invasive stage (OR, 1.42). Conclusions: Breast cancer patients with exposure to statins have proportionately fewer ER/PR-negative tumors that are of lower grade and stage. Although our data set cannot address whether statins affect the incidence of breast cancer, we show that statin use may influence the phenotype of tumors. This suggests a new potential strategy for breast cancer prevention, that of combining statins with agents that prevent ER-positive cancer (tamoxifen, aromatase inhibitors).