Cholesterol, breast cancer link builds

Kathleen Blanchard's picture
A cholesterol by-product acts like estrogen to fuel breast cancer growth and spread.

Duke University scientists have shown high cholesterol fuels the growth of breast cancer. The finding is important for women being treated for the disease and may be significant for helping with prevention.

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Cholesterol by-product spreads breast cancer

The reason high cholesterol helps the most common forms of breast cancer spread is because a by-product of the molecule acts like the hormone estrogen.

Senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke said in a media release: "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."

The good news is taking cholesterol-lowering drugs and making other lifestyle choices that include regular exercise and eating a heart healthy diet can stop the process.

The study finding, published in the journal Science, helps explain why obesity has been linked to the development and spread of breast and other types of cancer.

It’s also the first study to show the link between high cholesterol and metastasis that is fed by estrogen in 75 percent of cases of breast cancer.

What we already know about breast cancer risks

  • No environmental cause has been found for certain, but BPA is suggested as a contributor.
  • One out of 8 women will develop breast cancer in their lifetime
  • Age is the biggest risk factor for breast cancer.
  • Genes, breast density, alcohol and hormone therapy also contribute
  • Women who are overweight or obese are more prone to breast cancer.
  • Physical inactivity is linked to breast cancer.
  • Early menses and late menopause are associated with higher chance of cancer of the breast.

The study

For their study, researchers used mouse models that predict what happens in humans. The investigators were able to show 27HC is directly involved in tumor growth and the spread of breast cancer.

When the scientists stopped supplementing the mice with 27HC and treated them with antiestrogens the activity stopped.

To substantiate the findings, the researchers used human breast cancer tissue, finding the enzyme that makes 27HC in abundance in aggressive tumors.

They also found 27HC can be transported to tumors from other parts of the body.

High levels of 27HC could also explain breast cancer’s resistance to tamoxifen and aromatase inhibitors.

The next step is to find out if 27HC plays a role in other types of cancer. If other findings show cholesterol has a role in spread of breast or other types of cancer it could mean cholesterol-lowering drugs and other healthy lifestyle interventions could reduce a woman’s risk of the disease.

Past studies link cholesterol to breast cancer

A 1998 study showed a link between the development of breast cancer and high HDL cholesterol that is suggested to be protective against heart disease.

The earlier finding associating HDL cholesterol with breast cancer risk would pose a conundrum from postmenopausal women whose are not only at higher risk for breast cancer because of age, but also at increased risk for heart disease from declining estrogen.

The study that was also published in the journal Cancer Epidemiology, Prevention and Biomarkers looked at data from 95,000 women enrolled in the Kaiser Permanente Medical Care Program who were given a multiple phase health exam between 1964 and 1971.

Among 2000 women diagnosed with breast cancer, 200 were chosen for the study.

Thomas Jefferson University researchers subsequently discovered in findings published October, 2013 that HDL cholesterol receptors might promote breast cancer aggressiveness, found in mouse studies.

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Rather than suggesting HDL levels should be lower for women with the disease, the scientists noted there may be way to block the action of the receptor with pharmaceuticals.

The receptor, known as SR-BI was silenced in experiments with RNA, which in turn stopped breast cancer cells from migrating in addition to halting tumor growth.

The finding was published September, 2013 in the journal Breast Cancer Research.

Could cholesterol lowering drugs prevent or treat breast cancer?

Another interesting finding published in 2012 showed statins might help treat breast cancer.

The mechanism discovered by researchers at Columbia University still isn’t clear.

In the study, led by Carol Prives and published in the journal Cell Press, researchers used a 3D model and cancer cells grown in cultures.

The scientists noted more than half of cancers carry a mutation of the p53 gene that makes cancer aggressive. The mystery to researchers is what the p53 gene does to make cancer cells so invasive.

When the researchers treated the breast cancer cells with statins, they found mutant p53 was lowered and the 3D cells cultures began to grow more normally.

The study’s first author William Freed-Pastor was able to trace the changes to the mevalonate pathway in the body that builds cholesterol.

When the researchers analyzed breast tissue samples from patients, they found the same pathway also encourages human breast cancer tumors.

Some breast cancer cells treated with statins died in the lab, while others became more organized and less invasive.

Though the finding was preliminary, it also supports the notion that cholesterol has a role in breast cancer.

And indeed, women rare and aggressive inflammatory breast cancer (IBC) who taking statins were found in an observational study to survive longer, compared to women not taking the drugs.

The finding was presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium by investigators at University of Texas M. D. Anderson Cancer Center.

University of Pittsburgh researchers also found cholesterol-lowering drugs might have a protective effect against breast cancer.

For their investigation, 7528 white women age 65 years and older who participated in the Study of Osteoporotic Fractures at sites in Pittsburgh, Baltimore, Minneapolis and Portland were followed for seven years.

Jane Cauley, Dr.P.H., professor of epidemiology at the University of Pittsburgh Graduate School of Public Health said: “There is a significant difference in the percentage of breast cancer events between women who used lipid-lowering drugs and those who did not, and these findings have important public health implications given the widespread use of these medications today." Cauley suggested more studies.

The newest finding that cholesterol fuels the spread of breast cancer adds to a complex, but growing body of evidence that targeting cholesterol pathways could lead to new treatments and better outcomes for women battling the disease. It’s also possible that taking cholesterol lowering statin drugs could offer some protection against the most commonly occurring cancer in the world.

Image: Cells treated with 27HC
Courtesy: Duke University

Related:

  1. 10 things we learned about breast cancer in 2013
  2. How much exercise can cut a woman's chances of breast cancer?
  3. Osteoporosis drug stops breast cancer growth

Updated: 12/2/2013

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