The Contribution of Cholesterol and Its Metabolites to the Pathophysiology of Breast Cancer

As the most common cancer in women, one in eight will develop invasive breast cancer over their lifetime making it the second most common cause of cancer-related death among women. Of the many known risk factors for developing breast cancer, obesity stands out as prominent and modifiable. Interestingly, elevated cholesterol is highly associated with obesity and has emerged as an independent risk factor for breast cancer onset and recurrence. This indicates that cholesterol also contributes to the breast cancer pathogenicity of obesity. This review highlights our current understanding of the mechanisms by which cholesterol impacts breast cancer. Key preclinical studies have been highlighted, including the discussion of homeostatic control of cholesterol levels, signaling by cholesterol metabolites through the estrogen receptors, cholesterol formation of lipid rafts and subsequent signaling, and the potential roles of cholesterol in creating a proinflammatory tumor microenvironment. Future directions and avenues for therapeutic exploitation are also considered.