Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth

Metastasis is a leading cause of mortality in breast cancer, as metastatic disease is often aggressive and resistant to conventional treatments. Cancer cells that spread to distant organs can enter a dormant phase for extended periods, sometimes years or decades. During this dormant phase, cancer cells avoid immune and pharmacological response. Thus, new approaches are needed to prevent these disseminated cells from becoming lethal cancers. Statins are known inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that have been extensively used in patients with cardiovascular diseases to lower cholesterol. However, recent research has demonstrated their potential in anticancer therapies. Epidemiological evidence suggests that statins are associated with a reduction in breast cancer-specific mortality, although they do not appear to affect the incidence of primary tumors. In this review, we discuss the role of statins in metastasis and dormancy, their cytocidal and cytostatic effects and their interactions with different cell types in the tumor microenvironment. The exact mechanisms by which statins reduce mortality without influencing primary tumor growth remain unclear, also warranting further investigation into their potential role in metastasis and tumor dormancy, which could ultimately help patients to improve survival and quality of life.