What the researchers have found is that is isn't cholesterol itself, but a byproduct of cholesterol that spurs the spread and growth of breast cancer. When cholesterol is metabolized in the body, it produces a number of by products. One of those, 27-hydroxycholesterol (or 27HC) mimics the way that estrogen affects the body, and as a result, can "independently drive the growth of breast cancer.” The researchers from the same lab earlier found that 27HC behaved similarly to estrogen in animals. Estrogen, the primary female sex hormone, has been implcated in an estimated 75 percent of all breast cancers, according to the press release.
"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."
For their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect.
The researchers wanted to determine whether estrogen on its own was sufficient to promote breast cancer and whether controlling it could reverse the growth. McDonnell and colleagues used mouse models, highly predictive in humans as well to demonstrate the direct role of 27HC in growth and spread of breast tumor. When mice were treated with antiestrogens or with elimination of 27HC supplements in animals, cholesterol metabolite activity was greatly recudec.
The results of the mice study were supported by tests on human breast cancer tissue. Using human tissue, the researchers were able to show a direct link between an abundance of enzymes that make 27HC molecules and the aggressiveness of the tumor. This molecule can be transported to the tumor from other places in the body. “The worse the tumors, the more they have of the enzyme,” said Dr. Erik Nelson, a post-doctoral associate at Duke and lead author of the study, in the press release.
The studies were substantiated using human breast cancer tissue. An additional finding 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.
"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."
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 study suggests that beyond limiting risk of breast cancer by keeping cholesterol under control, women with breast cancer should work with their doctors to add cholesterol-fighting drugs like statins to their regime, in order to make sure that endocrine tharapies like tamoxifen and aromatase inhibitors actually retain their full efficacy.
source :
http://www.medicaldaily.com/high-cholesterol-provokes-breast-cancer-growth-and-spread-tumors-have-developed-new-source-fuel
http://www.sciencedaily.com/releases/2013/11/131128141357.htm
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