Statins and Breast Cancer: Future Directions in Chemoprevention.

Given the high incidence, morbidity and mortality associated with breast cancer, developing effective chemopreventive strategies is crucial. Clinicians must carefully identify both populations at risk who would benefit from chemoprevention, and interventions that are effective and safe. Tamoxifen and raloxifene, the two agents approved for breast cancer chemoprevention, and third generation aromatase inhibitors reduce only the incidence of hormone receptor-positive tumors. 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoAR) inhibitors, or statins, are well tolerated and approved for prevention of cardiovascular disease. In preclinical breast cancer models statins carry potent anti-neoplastic activity. Results from epidemiological and clinical studies, however, are conflicting and have not identified a strong relationship between statin use and reduced breast cancer incidence. These studies have several limitations and were not designed to detect modest effects in high-risk populations. Additional focused epidemiological and translational studies in high-risk populations are needed to justify and guide definitive large prospective trials.