Princeton Researchers Identify New Links Between High-Fat Diets and Aggressive Breast Cancer

A new study from Princeton University has uncovered how high-fat diets may make certain breast cancers more aggressive, offering new insight into how nutrition can influence tumour behaviour.

Published in APL Bioengineering, the research focused on triple-negative breast cancer, a form of cancer that is difficult to treat due to its lack of response to standard therapies.

Using advanced 3D tumour models, scientists simulated different dietary conditions by exposing cancer cells to various nutrients. While most diets showed little effect on tumour structure, those exposed to high levels of fatty acids and cholesterol behaved differently.

Instead of remaining compact, these tumours developed invasive, finger-like projections—features associated with aggressive cancers that spread into surrounding tissues and potentially metastasize.

Interestingly, tumour growth rates remained similar across all diet types. However, structural changes were significant in high-fat conditions. Cancer cells migrated outward from the tumour core, indicating increased invasive potential.

Researchers also identified a sharp rise in the activity of a gene called MMP1, which is known to break down collagen in surrounding tissues. This breakdown may create pathways that allow cancer cells to spread more easily.

In contrast, tumours exposed to high insulin, glycerol, ketones, or even a simulated ketogenic diet did not show the same aggressive structural changes. This was unexpected, as ketogenic diets are often thought to have protective effects against cancer. The findings suggest that, at least for this cancer type, fat itself—not just overall metabolism—may play a critical role in tumour invasiveness.

Researchers caution that these results are based on controlled lab models and may not fully replicate the complexity of the human body. However, the study highlights a potential biological link between dietary fat and cancer progression, opening new avenues for targeted therapies and personalized nutrition strategies in oncology.

REFERENCE: Kohram, M., et al. (2026). Fat promotes growth and invasion in a 3D microfluidic tumor model of triple-negative breast cancer. APL Bioengineering. DOI: 10.1063/5.0291646. https://pubs.aip.org/aip/apb/article/10/1/016111/3381798/Fat-promotes-growth-and-invasion-in-a-3D