Could High Cholesterol Increase the Risk of Breast Cancer?

A recent study looks at how high cholesterol can fuel the growth and spread of many types of breast cancer.

According to researchers from the Duke Cancer Institute, they found that by using mouse models and tumor cells, dietary changes or therapies can work to reduce cholesterol and lower the risk. 

"A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified," said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke, via a press release. "What we have now found is a molecule - not cholesterol itself, but an abundant metabolite of cholesterol - called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer."

Background information from the study notes that the hormone estrogen feeds of an estimated 75 percent of all estrogen--something that study researchers determined via 27-hydroxycholesterol--or 27HC--showed similar results in animals. 

For their study, researchers set out to determine whether this estrogen activity could promote cancer growth and metastasis on its own without, and whether controlling it would have a converse effect. 

McDonnell and colleagues used mouse models to demonstrate the direct involvement of 27HC in breast tumor growth as an aggressiveness of cancer that spread to other organs. They also examined the activity of this cholesterol metabolite that's inhibited when the animals were treated with antiestrogens or supplemented with 27HC was stopped. 

Additional findings showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. 

"The worse the tumors, the more they have of the enzyme," said lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke. Nelson said gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.

"This is a very significant finding," McDonnell said. "Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel."

Researchers believe these findings show a simple way to reduce the risk of breast cancer while keeping breast cholesterol levels low. 

More information regarding the study can be found via the journal Science.