How cutting fat could starve breast cancer

“The key here is that people have underestimated the importance of fat and lipids in the umbrella term that is obesity,” says Keren Hilgendorf, Ph.D., a researcher at the Huntsman Cancer Institute and assistant professor of biochemistry at UCLA. “But our study shows that breast cancer cells are actually addicted to fat, and the abundance of fat in obese patients is one reason why breast cancer is more prevalent.” “It is more aggressive in these patients.”

High blood fat levels, a condition known as hyperlipidemia, often accompanies obesity. Hilgendorf and her colleagues, Amandine Cheeks, Ph.D., assistant professor of nutrition and integrative physiology, and Greg Ducker, Ph.D., assistant professor of biochemistry, studied mice fed high-fat diets and other mice genetically engineered to develop hyperlipidemia without other hallmarks of obesity, such as elevated glucose and insulin. In both cases, excess fat alone was enough to accelerate tumor growth.

“The idea is that lipids, which make up the surface membrane of the cell, are like building blocks,” Cheeks says. “If the cell receives a signal to proliferate and more building blocks are available, the tumor will grow more easily. We see that a large amount of lipids enables this proliferation.”

When researchers lowered lipid levels in mouse models, tumor growth slowed, even in the presence of high glucose and insulin. While mice and humans have different metabolic processes, these findings may point to new therapeutic approaches or diet recommendations to help control cancer growth.

“We think this has therapeutic implications, because if you could just lower fats — which we already know how to do in patients, for example, with lipid-lowering drugs — that could be a way to slow the growth of breast cancer. If we can target these high levels of fats in the blood, the cancer will suffer because fats are no longer feeding the cancer,” says Hilgendorf. “But while our results in mice were impressive, there are clear limitations in projecting these results directly to human patients. Further research using human samples and patients will be necessary to confirm our hypotheses.”

The findings may also impact how obese patients and survivors manage their weight. Doctors often encourage weight loss to help reduce the risk of cancer coming back or spreading, but there is limited evidence about which diets are safest or most effective.

Many patients consider following the keto diet, which focuses on eating high in fat and very low in carbohydrates to stimulate a metabolic state called ketosis, in which the body burns fat instead of carbohydrates for energy.

The research team cautions that although such diets can promote weight loss, patients should carefully evaluate their overall metabolic health before adopting them.

“For patients diagnosed with breast cancer who have a high BMI, we recommend that they consult their doctor and develop a weight-loss plan as part of their treatment. If you have high cholesterol levels to begin with, consider a weight-loss plan or potential medications that can lower your lipid levels,” Ducker says. “As our study shows, diets like keto that are very high in fat can have serious unintended side effects — even causing tumor growth.”

The study suggests that fat may also fuel tumor growth in obese patients who have other types of breast, ovarian or colorectal cancer. The research team says the next steps will be to preclinically evaluate how anti-lipid drugs improve responses to chemotherapy. They also want to better understand how fats feed cancer cells.

Chakes, Dekker, and Hilgendorf also emphasize that their study is a specific type of cancer adapted to an obese environment, and that the keto diet may be beneficial for other types of cancer.

The results of the study were published in Cancer and metabolism. Renan Vieira, a doctoral student at the U, is the first author. The important research that occurs every day at Huntsman Cancer Institute is supported by the National Institutes of Health/National Cancer Institute, including Cancer Center Support Grants P30 CA042014, U01 CA272529-03S1, NCI UH2 CA286584, as well as the Huntsman Cancer Foundation.