Cholesterol Could Counteract Breast Cancer Treatment

Estrogen-mimicking molecules found in patients with high cholesterol reduce effectiveness of common breast cancer therapies

Released: 12/13/2013 10:00 AM EST
Source Newsroom: Newswise
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The following is a Newswise summary of an article originally posted by Duke Medicine on November 29, 2013, describing research findings recently published in the journal Science.

Newswise — Duke Medicine, DURHAM, N.C. — The hormone estrogen feeds an estimated 75 percent of all breast cancers, but in patients with high cholesterol, the presence of a certain molecule that mimics the structure of estrogen may lead to increased tumor growth, and inhibit the effects of common estrogen-blocking cancer therapies.

“What we have now found is a molecule – not cholesterol itself, but an abundant metabolite of cholesterol – called 27HC," said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke, "that mimics the hormone estrogen and can independently drive the growth of breast cancer.”

The research, published in the Nov. 29, 2013, edition of the journal Science, for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk.

“This is a very significant finding,” McDonnell said, because of the association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen.

"In essence, the tumors have developed a mechanism to use a different source of fuel,” McDonnell said.

The data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.

When an earlier finding in McDonnell’s lab determined that 27-hydroxycholesterol – or 27HC – behaved similarly to estrogen in animals, the studies were then substantiated using human breast cancer tissue. The test response in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. They also noted that 27HC could be made in other places in the body and transported to the tumor.

McDonnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. Additionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.

The next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if 27HC plays a role in other cancers, McDonnell said.

In addition to McDonnell and Nelson, study authors include 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.

The National Institutes of Health (K99CA172357) (R37DK048807) and the Department of Defense funded the study.


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