New Research Shows Obesity May Reshape How Breast Cancer Spreads
Key Takeaways:
- Obesity may alter how early, non-invasive breast lesions progress into invasive cancer, a University of Oklahoma study suggests.
- In women with obesity, progression was linked to inflammation, immune cell activity, metabolic changes and raised levels of the enzyme SULF2 – not the rapid cell division seen in women without obesity.
- The findings could improve risk prediction for women with DCIS and help reduce overtreatment.
A different route to invasive disease
Obesity may change how early-stage breast cancer becomes invasive, according to a study by University of Oklahoma researchers published in The American Journal of Pathology.
Obesity is already recognised as a risk factor for invasive breast cancer, but researchers have not fully understood how it helps early, non-invasive breast lesions develop into invasive cancer. A clearer picture of this process could strengthen physicians’ ability to predict and treat the disease.
In the study, breast cancers in women without obesity displayed the typical signs of turning invasive, including rapid cell division and an increased ability to invade neighbouring tissue. In women with obesity, however, the researchers identified a different set of biological changes that appeared to help the cancer become invasive.
The cancer environment became more inflamed, with the arrival of immune cells that advanced the growth of the tumour. The tumour cells also appeared better able to survive under stress, and there were changes in cellular metabolism – how the cells use nutrients for energy.
“This could be why women with obesity are at higher risk for invasive breast cancer,” said Bethany Hannafon, Ph.D., co-lead author of the study and an assistant professor in the Department of Obstetrics and Gynecology at the OU College of Medicine. “The changes that the cancer cells are undergoing are allowing them to survive and thrive.”
A cooperative cancer “neighbourhood”
The researchers also found differences in the “neighbourhood” of cells and tissues surrounding the cancer. Epithelial cells, where the tumour originally develops, co-opt other cells around them to create an environment that is even more conducive to cancer growth.
“In women with obesity, there is cooperation between all the cell types, not just the cancer cells, which helps an early pre-cancer to become an invasive breast cancer,” said co-lead author Elizabeth Wellberg, Ph.D., assistant professor in the Department of Pathology at the OU College of Medicine. “That may be an area of future study – can a drug or intervention that targets only one cell type interrupt the whole network of progression toward invasive cancer?”
The role of the enzyme SULF2
The research team additionally discovered higher levels of an enzyme called Sulfatase 2 (SULF2) in the tumour cells of women with obesity, suggesting that it may play an important part in cancer progression. SULF2 will be a further focus of future studies.
Why better DCIS risk prediction matters
Understanding what causes early, non-invasive tumours – known as ductal carcinoma in situ, or DCIS – to become invasive is important because not all women will go on to develop invasive cancer, yet they currently receive the same treatment.
“In women diagnosed with DCIS, about half will later develop invasive ductal carcinoma (IDC) that spreads into surrounding breast tissue. But we currently have no way of determining which women are most at risk. As a result, many women with DCIS receive the same treatments used for IDC, including surgery, radiation and sometimes hormone therapy. Overtreatment is a major concern, but if we had better ways of determining risk, unnecessary treatments could potentially be reduced,” Hannafon said.
While breast cancer survival rates have improved over the past two decades, the number of women diagnosed with invasive breast cancer has not declined – underscoring the need for better ways to predict and prevent disease progression.
A growing public health concern
The rising prevalence of obesity gives the findings added weight.
“Obesity is on the rise – 50% of Americans are expected to be obese by 2030,” said the paper’s first author, Cole Hladik, Ph.D., who worked in Hannafon’s lab while earning his doctorate. “That statistic further highlights the importance of considering a patient’s metabolic health alongside the biology of the tumor itself.”
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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.
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