Obesity-Linked Lipids Drive Aggressive Breast Cancer Growth in Mouse Models

Key Takeaways: 

• New research from the University of Utah reveals that lipids – fat molecules elevated in people living with obesity – can accelerate tumour growth in aggressive forms of breast cancer.
  
• The findings suggest that lipid-lowering therapies may slow cancer progression and that high-fat diets such as ketogenic regimens may worsen outcomes in some patients.
  
• Researchers caution that weight loss without addressing lipid levels is insufficient protection against obesity-associated cancers like triple-negative breast cancer.
  
  
  

Lipids identified as key driver in obesity-related breast cancer

A new study from the University of Utah’s Huntsman Cancer Institute (HCI) has found that lipids, a hallmark of obesity, play a significant role in fuelling tumour growth in an aggressive form of breast cancer. The research, funded by the National Cancer Institute and conducted using preclinical mouse models, highlights how lipid metabolism may be a crucial therapeutic target for individuals living with obesity who have or have survived breast cancer.

The findings suggest that breast cancer patients and survivors with obesity could benefit from therapies that lower lipid levels. Conversely, high-fat dietary approaches, such as the ketogenic diet, may have unintended adverse effects by increasing lipid availability to cancer cells.

“The key here is that people have underestimated the importance of fats and lipids in the all-encompassing term that is obesity,” explained Dr Keren Hilgendorf, assistant professor of biochemistry and investigator at HCI. “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.”

Focus on triple-negative breast cancer

The study focused on triple-negative breast cancer (TNBC) – a fast-growing and difficult-to-treat subtype that lacks receptors for oestrogen, progesterone, and HER2. TNBC is more common in women under 40 and in Black women, and it accounts for approximately 10 to 15 per cent of all breast cancer cases. This form of cancer is particularly prone to recurrence and metastasis.

A high level of lipids in the blood, known as hyperlipidaemia, is a frequent feature of obesity. Dr Hilgendorf and her colleagues, Dr Amandine Chaix and Dr Greg Ducker, both from HCI, examined how lipid levels influence tumour growth using specialised mouse models.

Lipid levels alone drive tumour growth

The researchers used two sets of models: one group of mice was fed high-fat diets, while another was genetically engineered to develop hyperlipidaemia without other typical markers of obesity, such as elevated blood glucose or insulin levels. In both cases, tumours grew faster when lipid levels were high.

“The idea is that lipids, which form the surface membrane of the cell, are like building blocks,” explained Dr Chaix, assistant professor of nutrition and integrative physiology. “If a cell receives the signal to proliferate and more building blocks are available, the tumour is going to grow more easily. We see that a high amount of lipids enables this proliferation.”

Importantly, when lipid levels were lowered – even in the presence of high glucose and insulin – breast cancer cell growth slowed down.

Potential implications for treatment and prevention

While the research was conducted in mice, the results point to potential therapeutic strategies for people with obesity and breast cancer.

“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,” said Dr Hilgendorf. “If we can target these high levels of fat in the blood, the cancer sufferers, because the lipids are no longer feeding the cancer. 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.”

Rethinking weight management in cancer care

These findings may also influence how clinicians guide people with obesity and breast cancer in managing their weight. While weight loss is commonly recommended to reduce recurrence risk, there is limited guidance on the best dietary approaches.

Some individuals turn to ketogenic diets, which are high in fat and low in carbohydrates, to induce ketosis – a state where the body uses fat rather than carbohydrates for energy. However, the new findings raise concerns about such diets in this patient group.

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

Beyond breast cancer: Broader implications

The research team believes that lipid-driven tumour growth may not be limited to breast cancer alone. Elevated lipid levels could also contribute to tumour progression in other cancers linked to obesity, such as ovarian or colorectal cancers.

The next stage of the research will investigate how anti-lipid drugs could improve the effectiveness of chemotherapy and explore the mechanisms through which lipids feed cancer cells.

Dr Chaix, Dr Ducker and Dr Hilgendorf emphasised that their results apply specifically to triple-negative breast cancer, and that ketogenic diets might still hold benefits for other forms of cancer. Nevertheless, their findings underscore the need for careful, evidence-based dietary guidance for people with obesity affected by cancer.