High Cholesterol Fuels Spread of Breast Cancer, Study Suggests

A new study involving mice may explain the link between high cholesterol and breast cancer, particularly in postmenopausal women.

Researchers from the Duke Cancer Institute previously discovered that a byproduct of cholesterol known as 27HC behaves like estrogen, a hormone believed to fuel up to 75 percent of all breast cancers.

In the new study published in the journal Science, the researchers used mice to demonstrate for the first time the direct involvement of the molecule in breast tumor growth.

"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. "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."

In addition to fueling breast cancer, 27HC is a key player when it comes to the aggressiveness of the cancer in its spread to other organs.

"The worse the tumors, the more they have of the enzyme," lead author Erik Nelson, PhD, a post-doctoral associate at Duke, said in a statement.

The cholesterol metabolites activity was mitigated, however, when the researchers treated the animals with antiestrogens or when supplements of 27HC ceased.

In using human tissue, the scientists also found that 27HC could be manufactured in other places in the body and then transported to the tumor.

According to Nelson, gene expression studies suggested a possible association between exposure to 27HC and increased resistance to the antiestrogen tamoxifen. In addition, the molecule may inhibit the effectiveness of aromatase inhibitors, one of the most common class of breast cancer drugs.

"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."