Statins and breast cancer: may matrix metalloproteinase be the missing link.

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors), cholesterol-lowering agents widely prescribed for cardiovascular health, have been shown to exert several pleiotropic effects. Although some studies reported that statins have no effects on malignancies of any kind, results of several epidemiologic and in vitro studies highlighted that statins exert anticancer activity in various cell types, showing that long-term therapy inhibits the incidence and/or progression of some human tumours. In particular, in the present overview we focused the attention on a neglected aspect of the pleiotropic functions of some lipophilic statins, suggesting that the possible mechanism of matrix metalloproteinase downregulation arises from prolonged lowering of circulating cholesterol. Our hypothesis may explain the literary findings about the phenomenon of switching of breast cancer phenotypes by statins, shedding the basis of future epidemiologic and basic science studies about the role of circulating and/or tumor-resident cholesterol in the initiation and progression of breast cancer.