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High Cholesterol Fuels Growth and Spread of Breast Cancer

A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers have found.

Published: 29th November 2013 02:37 PM  |   Last Updated: 29th November 2013 02:46 PM   |  A+A-

breast-cancer-ribbon
By PTI

A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers have found.

Scientists from the Duke Cancer Institute also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule.

The research 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, they 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," said senior author Donald McDonnell, 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," McDonnell said.

The hormone estrogen feeds an estimated 75 per cent of all breast cancers. In a key earlier finding from McDonnell's lab, researchers determined that 27-hydroxycholesterol – or 27HC - behaved similarly to estrogen in animals.

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.

Using mouse models that are highly predictive of what occurs in humans, McDonnell and colleagues demonstrated the direct involvement of 27HC in breast tumour growth, as well as the aggressiveness of the cancer to spread to other organs.

They also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of 27HC was stopped.

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 tumour 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 tumour.

Lead author Erik Nelson, a post-doctoral associate at Duke 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.

The study was published in the journal Science.


Read more about breast cancer:

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Obese women at higher risk of breast cancer

Aus scientists find new breast cancer gene

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One in 30 likely to develop Breast Cancer: Experts

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