A byproduct of cholesterol that acts like estrogen explains the link between high cholesterol and breast cancer

The link between high cholesterol and breast cancer can now be explained.

It is not the cholesterol itself, but a "byproduct of cholesterol (that) functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancer," researchers at the Duke University Cancer Institute report, according to Newswise.

Estrogen is known to "feed an estimated 75 percent of all breast cancers," Newswise reports. So basically, cholesterol creates a "byproduct" that acts like estrogen and "feeds" the breast cancer, the researches concluded.

This is the first time a link between high cholesterol and breast cancer has been explained, especially in post-menopausal women, according to the study, which also suggests that changes in diet or taking statins and other medication to reduce cholesterol may offer "simple ways to reduce breast cancer risk," Newswise reports.

Although studies have shown a connection between obesity and breast cancer, as well as high cholesterol and breast cancer, the reason for these connections had not been explained, 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.”

The researchers also found that the more enzyme that makes the cholesterol byproduct that is present, the more aggressive the tumor.

When test animals took anti-estrogen drugs such as tamoxifen, or when they quit receiving the cholesterol byproduct, the cancer was inhibited, according to Newswise.

Nelson said in the article that there was also a potential association between the cholesterol byproduct and the development of resistance to the anti-estrogen tamoxifen. Data also suggest the cholesterol byproduct may reduce the effectiveness of commonly used breast cancer therapies.

These findings suggest that women who have breast cancer and high cholesterol who take statins will  have increased benefit, Newswise reports, because it will decrease their resistance to commonly used breast cancer therapies.

Further research will "include clinical studies to verify the suggested potential outcomes and to determine if this cholesterol byproduct plays a role in other cancers," McDonnel said.

New guidelines for cholesterol management spark controversy; faulty risk calculator could lead to over-prescribing statins

The American College of Cardiology and the American Heart Association released new guidelines for cholesterol management, a new formula to assess heart attack and stroke risk, and guidelines for lifestyle modifications and weight management to reduce heart attack and stroke risk.

“These guidelines will be helpful to all physicians and their patients, but they will be particularly relevant in Kentucky, where nearly 70 percent of Kentuckians are overweight or obese, we are the third highest state in rates of high blood pressure, five Kentucky counties are among the least active in the U.S. and the incidence of diabetes is above the national average,” Dr. Susan Smyth, director of the Gill Heart Institute at the University of Kentucky, said in an e-mail.

However, some experts have questioned the new guidelines, and the new formula for calculating cardiovascular risk appears to overstate the risk value used to determine who should receive cholesterol-lowering statin drugs.

"There may be no single perfect score that we can use to give statins the 'thumbs up' or 'thumbs down' for our patients without established cardiovascular disease," Smyth said. "Ultimately, physicians have many different tools at their disposal to evaluate CV risk in their patients, and they will review all of the available evidence to make a determination about who may be likely to benefit from statin therapy."

The new guidelines also change how statins should be prescribed. The drugs have been given to lower cholesterol to a specific numerical value, but now it is suggested that moderate to high doses of statins be given to patients who fall within four identified groups of patients who have been determined to get the most benefit from the drug:

• already diagnosed with heart disease or stroke
• with an LDL {"bad" cholesterol) of 190 mg/dL or higher, who may have genetic risk
• aged between 40 and 75, with Type 2 diabetes and high LDL levels, but without heart disease or stroke
• with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75, without heart disease or stroke, but with high LDL levels.  

Instead of focusing strictly on patients' LDL and total cholesterol, the new guidelines suggest physicians treat patients based on their overall risk of heart disease or stroke, of which cholesterol levels are just one part, according to the report.

The guidelines in the report also call for lifestyle modification, including adhering to a heart-healthy diet, which includes vegetables, fruits, whole grains, low-fat dairy, poultry, fish, beans and healthy oils and nuts; 30 to 40 minutes of exercise three to four times a week; avoidance of tobacco products, and maintenance of healthy weight.

The guidelines use a cardiovascular risk calculator that considers age, race, sex, diabetes, smoking habits, blood pressure and low HDL, or "good" cholesterol levels, among other considerations.

But a problem has been identified with the risk calculator, so worrisome that a past president of the College of Cardiology called for a halt to the implementation of the new guidelines, reports Gina Kolata of The New York Times. The calculator appears to overestimate the risk group so greatly, Kolata reports, that it could mistakenly suggest that millions more people should be candidates for statin drugs.

"It's stunning," the cardiologist, Dr. Steven Nissen, chief of cardiovascular medicine of the Cleveland Clinic, told Kolata. "We need a pause to further evaluate this approach before it is implemented on a widespread basis."

After an emergency, closed-door meeting on Saturday night, the two organizations that published the guidelines said "that while the calculator was not perfect, it was a major step forward, and that the guidelines already say patients and doctors should discuss treatment options rather than blindly follow a calculator," Kolata reports.

Dr Sidney Smith, the executive chairman of the guideline committee, told Kolata that "the association would examine the flaws found in the calculator and determine if changes were needed."

Two Harvard Medical School professors, Dr. Paul M. Ridker and Dr. Nancy Cook, had pointed out the calculator was not working among the populations it was tested on by the guideline makers a year earlier, during an independent review for the National Institutes of Health's National Heart, Lung, and Blood Institute, which originally developed the guidelines, Kolata reports.

Dr. Donald Lloyd-Jones, co-chairman of the guidelines task force and chairman of the department of preventive medicine at Northwestern University, told Kolata that "the committee thought the researchers had been given these results."

Ridker and Cook evaluated the calculator again after they saw the guidelines and found that it over- predicted risk by 75 to 150 percent, depending on the population, Kolata reports. They wrote in The Lancet, a British medical journal, that the miscalibration be "reconciled and addressed" before implementation, saying: "If real, such systematic overestimation of risk will lead to considerable over-prescription."

Some doctors are concerned that because many people are already "leery of statins, the public would lose its trust in the guidelines or the heart associations," Kolata reports. Currently, it is only obvious that those in the highest risk groups, such as those who have heart attacks, strokes or have diabetes, should take statins, she reports.

UK and Purdue researchers find a compound in watermelon that fights 'bad' cholesterol and arterial plaque in lab rats

A study from the University of Kentucky and Purdue University showed that mice fed a diet including watermelon juice had lower weight, cholesterol and arterial plaque than a control group. The findings, reported in the Journal of Nutritional Biochemistry, suggest that citrulline, a compound found in watermelon, plays a role in cardiovascular health. "We were interested in citrulline because previous studies showed that it may lower blood pressure,"  Shubin Saha, a Purdue Extension vegetable specialist and study co-author, told Medical Xpress. "We didn't see a lowering of blood pressure, but these other changes are promising."

"The researchers fed two groups of mice diets high in saturated fat and cholesterol," MX reports. "Half the mice received water containing 2 percent watermelon juice, while the others received the same amount of water supplemented with a solution that matched the carbohydrate content of the watermelon juice. The mice that consumed watermelon juice gained about 30 percent less weight than the control group and had about 50 percent less LDL cholesterol - the so-called bad cholesterol. The experimental group also had about a 50 percent reduction in plaque in their arteries, as well as elevated levels of citrulline." Sibu Saha, a professor of surgery at UK, explained that the researchers are not sure at what molecular level the citrulline is working, but that is their next step.

Shubin Saha was excited about the dual benefit of the findings. "Twenty percent of each year's watermelon crop is wasted either because the fruit is visibly unappealing to consumers or because some growers find it too expensive to pay for harvesting as prices drop during the height of watermelon season." The wasted melons, he explained, could be put to use extracting these very beneficial compounds.  (Read more)

Study finds 'the link between cholesterol and cancer is clear'

University of Rochester Medical Center scientists have verified a link between cholesterol and cancer with new genetic evidence, raising the possibility that cholesterol medications such as statin drugs could be used for cancer prevention or to augment existing cancer treatment.

"The link between cholesterol and cancer is clear," senior study author Hartmut Land said, "but it's premature to say that [cholesterol-lowering drugs] are the answer." Still, The Times of India reports that the data gathered by the research team at the James P. Wilmot Cancer Center at URMC "supports several recent population-based studies that suggest individuals who take cholesterol-lowering drugs may have a reduced risk of cancer, and, conversely that individuals with the highest levels of cholesterol seem to have an elevated risk of cancer." 

Millions of Americans take cholesterol-lowering drugs prescribed by physicians. The drugs work by blocking the action of key enzymes in the liver, which synthesizes cholesterol. The Times story explains that "clinical trials also are evaluating statins as a tool against cancer, and some previous studies suggest that when used in combination with chemotherapy, statins might make chemotherapy more effective by sensitizing certain cancer cells to chemotherapy-induced cell death. Land, however, urges caution and further study. Doctors do not know the appropriate statin dose for cancer prevention or treatment of cancer-related conditions. Side effects cannot be ignored either, and little research has distinguished between the responses among people who take statins."

See the study in the online journal Cell Reports by clicking here.