Cholesterol is a waxy, fat-like substance found throughout the body, including the blood. High circulating cholesterol has been linked to increased risk of breast cancer in women. Normal breast cells respond to low-density lipoprotein (LDL, the "bad" cholesterol) by increasing proliferative and pro-inflammatory signaling, thereby setting the stage for breast cancer development. Tamoxifen works, in part, by reducing cholesterol.
Cholesterol has been shown to promote and accelerate mammary tumor formation in animal models of breast cancer. Mice fed a high cholesterol diet tend to develop larger tumors that are faster growing and metastasize more easily compared to mice on control diets. In addition, an increase in dietary cholesterol appears to heighten tumor aggressiveness in mice. High cholesterol also has been shown to induce angiogenesis and accelerate tumor growth in a mouse model of triple negative breast cancer. Now a new study has shown how cholesterol acts to promote breast cancer growth and metastasis.
Low cholesterol can also be associated with breast cancer
While high cholesterol has been linked to increased risk of breast cancer in women, there is also some evidence that low cholesterol is also associated with breast cancer. This might be because circulating cholesterol levels are reduced during tumor development (because of increased use of cholesterol by tumors).
Statin drugs and breast cancer
Statin drugs, which are used to treat high cholesterol, have been reported to reduce breast cancer risk in some studies but not in others. Similarly, breast cancer recurrence might be influenced by statin use, but the evidence is mixed. As a result, the topic of statin use and its association with breast cancer is controversial. Currently, it is not currently possible to determine which breast cancer survivors could benefit from statin use. However, for those who need to take statins, lipophilic statins such as Zocor and Lipitor appear to be the best choice.
Latest research shows how cholesterol promotes breast cancer
The study referenced at the beginning of this news article was designed to investigate the effects of cholesterol on tumor development and pathology. High cholesterol is associated with reduced treatment response to endocrine treatments such as aromatase inhibitors. In the study, the authors used mouse models of breast cancer to show that 27-hydroxycholesterol, a primary product of cholesterol metabolism that binds to both estrogen and liver X receptors, increased both ER-dependent tumor growth and LXR-dependent metastasis.
Additional analysis demonstrated that the tumor-promoting effects of cholesterol required its conversion to 27-hydroxycholesterol by the cytochrome P450 oxidase CYP27A1: the tumor-promoting effects were reduced by treatment with CYP27A1 inhibitors. Using human breast cancer tissue specimens, the authors also found that CYP27A1 expression levels were linked to tumor grade: tumor cells and tumor-associated macrophages both exhibited high expression levels of the enzyme in high-grade tumors. The authors conclude that lowering cholesterol levels or interfering with its conversion to 27-hydroxycholesterol may be a useful strategy to prevent or treat breast cancer.