Fat may make certain aggressive breast cancers more invasive, offering researchers a clearer direction for future treatments and raising new questions about how diet influences cancer behavior, according to a study published recently in APL Bioengineering.
Scientists at the university found that while tumors exposed to high-fat conditions did not grow faster, they changed shape in ways linked to cancer spread. Specifically, triple-negative breast cancer tumors developed hollow, branch-like extensions that reached into surrounding tissue, a hallmark of aggressive disease. This type of cancer is known for being difficult to treat because it does not respond to many standard therapies.
“Aggressive cancers have these tendrils, and it’s the leading edges that end up invading into our normal tissues and making it into either a lymphatic or a blood vessel and escaping and metastasizing,” wrote Celeste Nelson, Ph.D., the study’s principal investigator and the Wilke Family Professor in Bioengineering and a professor of chemical and biological engineering at Princeton.
To better understand the process, researchers created 3D tumor models that mimic the human body more closely than traditional lab methods. They exposed these tumors to different nutrient conditions, including fats, insulin, glycerol and ketones. Only the tumors exposed to fatty acids and cholesterol showed these invasive structural changes. Tumors grown under other conditions remained compact and less aggressive in appearance.
Read more about the causes and risk factors of breast cancer
The study also identified a possible biological mechanism behind these changes. Tumors in high-fat conditions showed increased activity of a gene called MMP1, which helps break down collagen in surrounding tissue. This breakdown may allow cancer cells to move more easily into nearby areas and potentially spread. While the researchers believe fat may play a role in activating this gene, they have not yet proven a direct cause-and-effect relationship.
One unexpected finding involved the ketogenic diet, which is high in fat and low in carbohydrates. Researchers had expected it might protect against tumor growth, but the model showed no clear benefit compared to baseline conditions. This suggests that any potential effects of such diets may depend on factors not included in the model, such as interactions with other cells in the body.
For patients, these findings do not immediately change treatment recommendations but highlight the growing importance of understanding how diet may influence cancer behavior. The research points to MMP1 as a potential target for future therapies and suggests that dietary fat could play a role in how aggressively some cancers behave. More studies, especially in humans, are needed before making specific dietary guidelines, but the work opens a new path toward more personalized cancer care.
Sign up here to get the latest news, perspectives, and information about breast cancer sent directly to your inbox. Registration is free and only takes a minute.