Is cholesterol a risk factor for breast cancer incidence and outcome?

Cholesterol plays important roles in many physiological processes, including cell membrane structure and function, hormone synthesis, and the regulation of cellular homeostasis. The role of cholesterol in breast cancer is complex, and some studies have suggested that elevated cholesterol levels may be associated with an increased risk of developing breast cancer, while others have found no significant association. On the other hand, other studies have shown that, for total cholesterol and plasma HDL-associated cholesterol levels, there was inverse association with breast cancer risk. One possible mechanism by which cholesterol may contribute to breast cancer risk is as a key precursor of estrogen. Other potential mechanisms by which cholesterol may contribute to breast cancer risk include its role in inflammation and oxidative stress, which have been linked to cancer progression. Cholesterol has also been shown to play a role in signaling pathways regulating the growth and proliferation of cancer cells. In addition, recent studies have shown that cholesterol metabolism can generate tumor promoters such as cholesteryl esters, oncosterone, 27-hydroxycholesterol but also tumor suppressor metabolites such as dendrogenin A. This review summarizes some of the most important clinical studies that have evaluated the role of cholesterol or its derivatives in breast cancer. It also addresses the role of cholesterol and its derivatives at the cellular level.