How a basic building block of the body could prevent breast cancer

Carol Fabian, M.D., co-leader of The University of Kansas Cancer Center Cancer Prevention Program and the Morris Family Endowed Chair in Cancer Prevention, is leading a study for women with a higher risk of breast cancer that focuses on two natural approaches to preventing breast cancer: weight loss and omega-3 fatty acids EPA and DHA.

"Women in this study have a family history of breast cancer or a previous biopsy showing precancerous breast disease," said Dr. Fabian. "Prior to entering the study, they have their breast tissue tested and are found to have too many cells in the breast ducts, called hyperplasia. Their blood and breast tissues are also tested for other risk factors for breast cancer."

All the women in the trial are placed on a calorie-restricted diet, along with support from a nutritionist and online weight loss and exercise tracking tools. Their goal is to lose 10 percent of their body weight in the first six months and maintain it in the second six months. In addition, half of the participants are given a high-dose omega-3 supplement while the other half are given a placebo. Their blood and breast tissue is tested again at six and 12 months. Periodically, the women's biomarker levels will be tested.

Research has already shown a link between obesity and breast cancer risk. Abnormal fat cells increase the amount of hormones as well as inflammation in the body. The majority of breast cancers are fueled by hormones such as estrogen, and it is likely that some breast cancers are stimulated by inflammation as well.

Previous studies by Dr. Fabian and her team showed that if an overweight or obese person loses at least 10 percent of their body weight, there's a reduction in hormone production and fewer inflammatory biomarkers. "The challenge is keeping those extra pounds off," she said, as anyone who has lost any amount of weight knows.

As a result, Dr. Fabian is seeing if higher doses of the omega-3 fatty acids EPA and DHA would help with weight loss maintenance as well as favorably reduce risk biomarkers for breast cancer. Omega-3 fatty acids have multiple important body functions, such as cell signaling, proper immune system function and improving cognitive function. Higher dose EPA and DHA (fish oil supplements) are already used for prevention of cardiovascular diseases and to help with inflammatory disorders such as rheumatoid arthritis and irritable bowel disorder. The omega-3 fatty acids are primarily found in fatty cold water fish such as salmon and leafy green vegetables, which typically aren't eaten in abundance.

A schema of Dr. Fabian's omega-3 and weight loss trial and when the presence of breast cancer biomarkers is measured.

Dr. Fabian first got the idea to study omega-3 fatty acids and how they might affect cancer after hearing about a "miracle" food for dogs with mammary cancer or lymphoma.

"Six years ago I heard about this Topeka, Kan., company named Hill's Pet Nutrition, which was founded by veterinarians and manufactured a special diet dog formulation. It didn't cure cancer, but it helped dogs with these cancers of an advanced stage live for a long time," said Dr. Fabian. "So I asked what was in it, and they said it was a really high dose of omega-3."

The specific omega-3 fatty acids that are most beneficial to humans are DHA and EPA, which are mostly found in fatty, cold water fish. The average person only ingests about 100 milligrams of EPA and DHA a day when they should be getting about 30 times that amount.

Dr. Fabian has already done a study looking at how omega-3 fatty acids work in pre- and postmenopausal women with an increased risk for breast cancer. The amount of a specific inflammatory biomarker, MCP1, was decreased in the women taking an omega-3 supplement. Previous research has also shown that omega-3 in particular seems to affect similar reward brain pathways as weight loss does.

Does this mean taking an omega-3 supplement can help people who have already lost weight keep it off by keeping those brain pathways active?

"Omega-3 seems to affect the same pathways in the brain as losing weight," explained Dr. Fabian. "If we could help people who have lost weight from gaining it back, that would be a big help in reducing their cancer risk. We want to see if omega-3 can improve the biomarker risk factor along with the weight loss and if it will make the maintenance phase easier."

Several scientists are working with Dr. Fabian on this project, including Bruce Kimler, PhD, in Radiation Biology, and Steve Hursting, PhD, MPH, a basic scientist working on obesity from the University of North Carolina at Chapel Hill. Susan Carlson, PhD, is measuring fatty acid levels, Christie Befort, PhD, and Debra Sullivan, PhD, are in charge of the weight loss aspects and Jennifer Klemp, PhD, is examining quality of life. Two unique features of this grant are to determine whether EPA and DHA change bacteria in the colon associated with inflammation and whether these omega -3 fatty acids change reward center responses to food.

"Certain types of bacteria increase inflammation in the colon, which increases the risk for colon cancer and likely other diseases too," said Dr. Fabian. "We're seeing if anything changes with the omega-3, and I'm convinced it will." Shadid Umar, PhD, KU Cancer Center member and associate professor in molecular and integrative physiology, is determining whether EPA and DHA have a favorable effect on gut bacteria.

Women are also undergoing a functional brain MRI after six months of weight loss with or without the EPA and DHA. Cary Savage, PhD, director of the Center for Health Behavior Neuroscience at the University of Kansas Medical Center, Laura Martin, PhD, associate director of functional MRI and William Brooks, PhD, director of the Hoglund Brain Imaging Center, are looking at the brain's response to food after weight loss via MRIs.

"Mice studies done by Dr. Hursting have shown that some of these important cancer-causing pathways are stimulated in obese mice," said Dr. Fabian. "When you lose weight, these pathways partially, but not fully, normalize. We hope that omega-3 may help with this process."