Fatty acids found to be a primary driver of triple-negative tumor growth

A team from Huntsman Cancer Institute at the University of Utah (the U) has found that triple-negative breast cancer is fueled by lipids and that these fatty acids are a key feature of obesity that promote tumor growth.

Their National Cancer Institute-funded research, conducted in preclinical mouse models, suggests that breast cancer patients and survivors with obesity could benefit from lipid lowering therapies-and that they should avoid high-fat weight loss regimens like ketogenic diets.

The key here is that people have underestimated the importance of fats and lipids in the all-encompassing term that is obesity. But our study shows that breast cancer cells are really addicted to lipids, and the abundance of lipids in patients with obesity is one of the reasons that breast cancer is more prevalent and more aggressive in these patients."

Keren Hilgendorf, PhD, Investigator, Huntsman Cancer Institute

Hilgendorf is also an assistant professor of biochemistry at the U. 

A high amount of lipids in the blood, known as hyperlipidemia, is a common condition associated with obesity. Hilgendorf and her colleagues Amandine Chaix, PhD, Huntsman Cancer Institute investigator and assistant professor of nutrition and integrative physiology at the U, and Greg Ducker, PhD, Huntsman Cancer Institute investigator and assistant professor of biochemistry at the U, conducted their research by analyzing mouse models on high-fat diets.

They also used models that were engineered to have hyperlipidemia without other key markers of obesity, like high glucose and insulin levels. In these models, the high lipids alone were enough to accelerate tumor growth.

"The idea is that lipids, which form the surface membrane of the cell, are like building blocks," added Chaix. "If a cell receives the signal to proliferate and more building blocks are available, the tumor is going to grow more easily. We see that a high amount of lipids enables this proliferation." 

In this particular model, lowering the amount of lipids, in the presence of high glucose and insulin levels, was enough to slow down breast cancer cell growth. Mice and humans have important metabolic differences, but if the results in mice hold true in people, they could lead to better therapies and diet recommendations to slow cancer growth.

"We think this has therapeutic implications, because if you could just lower the lipids-which we already know how to do in patients, for example, with lipid-lowering medication-that could be a way to decelerate breast cancer growth. If we can target these high levels of fat in the blood, the cancer suffers because the lipids are no longer feeding the cancer," stated Hilgendorf. "But while our results in mice were striking, there are clear limitations in directly projecting these findings onto human patients. More research using human samples and patients will be necessary to confirm our hypotheses."

Their findings could also impact how breast cancer patients and survivors with obesity approach weight management. Clinicians often recommend that patients lose weight as part of their treatment, as obesity can be a factor in increased risk of cancer spread or disease recurrence. But there are few evidence-based guidelines as to which diets are best.

Some patients may turn to the popular keto diet, which consists of a high-fat and low-carbohydrate intake. The goal is to reach a metabolic condition called ketosis, where the body uses fat instead of carbohydrates as a source of energy.

The researchers say this approach could lead to weight loss, but patients need to consider the whole picture of their metabolic health.

"For patients who are diagnosed with breast cancer and have an elevated BMI, we would advise them to consult their physician and develop a weight loss plan as part of their treatment. If you have high cholesterol levels to start with, think about a weight loss plan or potential pharmaceuticals that could lower your lipid levels," added Ducker. "As our study shows, diets like keto that are very high in fat can have serious unintended side effects-even causing the tumor to grow."

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

Chaix, Ducker, and Hilgendorf also stressed that their study is one specific type of cancer adapting to an obese environment, and that the keto diet may be beneficial for other types of cancer.