Many breast cancers may be linked with cholesterol byproduct, study finds

DURHAM, N.C. — Studies have long shown a link between obesity and breast cancer, and now scientists at Duke Cancer Institute may have found one important explanation: a byproduct of cholesterol that fuels tumors in some of the most common forms of the disease.

The finding could point the way to simple methods to reduce breast cancer risk, including using cholesterol-lowering drugs such as statins and eating a healthier diet. It also suggests that using statins could make regimens for treating many breast cancers more effective.

Results of the study, which are considered early because research relied on mice and cancer tissue, are being published in Friday’s edition of the journal Science.

Obesity is implicated in a number of human cancers, and the data linking it to breast cancer in post-menopausal women are particularly strong, said Donald McDonnell, chairman of the Department of Pharmacology and Cancer Biology at the Duke University School of Medicine and senior author of the paper.

But until now, there was no understanding of the mechanism involved, so it was hard to know how to attack the problem, McDonnell said.

The researchers wondered how large a role was played by the high cholesterol levels often associated with obesity.

Using human tumor cells and mice bred to be especially vulnerable to breast cancer, they found that a molecule called 27-
hydroxycholesterol or 27HC, which is converted from cholesterol in the body, fuels the growth and spread of tumors.

“But if you inhibit the conversion of cholesterol to this molecule, nothing bad happens,” McDonnell said.

They also determined that raising cholesterol levels raised risk, and that reducing cholesterol had an effect similar to suppressing its dangerous byproduct, resulting in tumors that grew at significantly slower rates.

Also, the study data suggest that tumors aren’t reliant on the presence of 27HC in the blood; they are capable of producing large amounts of an enzyme that converts cholesterol to 27HC. That means that the tumors can essentially feed their own growth.

The molecule appears to mimic effects of the hormone estrogen on the cancers. About 75 percent of breast cancers are at least partly fueled by estrogen.

McDonnell said a startling moment in the research came when the scientists discovered that preventing formation of 27HC in the special breast-cancer mice delayed the appearance of their first tumor by 50 days, and that after the first tumor formed, the mice lived an average of 40 percent longer than those that could still make the molecule.

“That really got our attention,” McDonnell said.

The next steps include studying data that have been generated in a large, long-term study of humans to see how high cholesterol levels and the use of statins may have affected breast cancer among the women enrolled, McDonnell said.

Also, the researchers want to know how adding statins to the therapies for breast cancer patients might affect the outcome of treatment.

Another avenue to explore, he said, is potential links between 27HC and other cancers, such as that of the uterus.

The study was funded by the National Institutes of Health and the Defense Department.

Besides McDonnell, the authors include Erik Nelson, Suzanne E. Wardell, Jeff S. Jasper, Sunghee Park, Sunil Suchindran, Matthew K. Howe, Nicole J. Carver, Ruchita V. Pillai, Patrick M. Sullivan, Varun Sondhi, Michihisa Umetani and Joseph Geradts.

— McClatchy-Tribune

 
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