November 30, 2013
High Cholesterol Increases Breast Cancer Risk
Rebekah Eliason for redOrbit.com - Your Universe Online
Using mouse models and tumor cells, this is the first discovered link connecting high cholesterol with breast cancer. The information is an exciting new step suggesting a simple and accessible treatment of dietary change or therapy focusing on cholesterol reduction to lower breast cancer risk.
Donald McDonnell, PhD, chair of the Department of Pharmacology and Cancer Biology at Duke and senior author of the study said, “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. 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.”
Approximately 75 percent of all breast cancers are fed by the hormone estrogen. McDonnell’s lab previously made a key discovery showing that 27-hydroxycholesterol (27HC) behaves in animals similar to estrogen.
The current study was designed to discover if estrogen alone could be responsible for breast cancer growth and metastasis. Researchers also set out to determine if controlling estrogen would have a converse effect.
With the help of mouse models, McDonnell and his team demonstrated how 27HC has direct involvement in breast tumor growth along with the aggressiveness in which cancer spreads to other organs. They also showed how animals treated with antiestrogens or that stopped 27HC supplementation had inhibited activity of the cholesterol metabolite.
The study’s findings were confirmed through study of human breast cancer tissue. Additionally, human tissue demonstrated direct correlation between the aggressive nature of the tumor and the quantity of the enzyme responsible for 27HC molecule. Researchers also found the 27HC molecule could be produced in other parts of the body and then transported to the cancerous tumor.
“The worse the tumors, the more they have of the enzyme,” said lead author Erik Nelson, PhD, a post-doctoral associate at Duke. Nelson explained how gene expression studies exposed the potential connection between exposure to 27HC and the development of resistance to the antiestrogen treatment tamoxifen. One of the most common breast cancer therapeutics is aromatase inhibitors and the new data suggests increased 27HC possibly reduces the treatment effectiveness.
“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.”
McDonnell explained that the discoveries suggest simply keeping cholesterol in check by statins or a healthy diet may be an easy way to reduce breast cancer risk. Also, women in the middle of breast cancer treatments should take statins to delay or prevent developing resistance to endocrine therapies using tamoxifen or aromatase inhibitors.
Researchers plan to further this study through clinical studies to verify the outcomes and establish the role 27HC plays in other cancers.
This study was published November 29, 2013 in the journal Science.