High-fat diet promotes breast cancer metastasis

Obesity is associated with an increased risk of developing breast cancer, as well as a greater likelihood of cancer spreading to other organs. However, the reasons for this link are still not well understood. Researchers from Spain’s National Cancer Research Center (CNIO) have presented new data, finding that high-fat diets activate mechanisms that promote metastasis.

The study, led by Héctor Peinado, head of the CNIO’s Microenvironment and Metastasis Research Group, was conducted in animal models of triple-negative breast cancer developing metastases to the lungs. The study is published in the journal Nature Communications.

For cancer to spread to other organs, many tumor cells must leave the primary tumor, travel through the bloodstream, settle and multiply in another organ. Sometimes the primary tumor sends molecules that alter the target organ in advance and prepare a nestlike structure to house the tumor cells: this is the so-called “pre-metastatic niche” in which the tumor cell can take root and develop metastases.

In their new study, the CNIO team showed that in mice that are obese due to excessive consumption of fatty foods, changes occur that promote the creation of a pre-metastatic niche, in this case in the lungs. In particular, platelet activation and blood clotting ability are increased; in addition, fibronectin, a protein that connects lung tissue cells, is activated.

Platelet armor

Obesity is known to promote blood clotting, a process that depends on the number of platelets. Indeed, in animals fed a fatty diet, cells rejected from a primary tumor are surrounded by more platelets during their journey through the blood than in mice with a normal diet.

One hypothesis is that platelets may prevent the body’s defenses from detecting cancer cells: platelets form an “armor around tumor cells, preventing the immune system from recognizing and destroying them.

A fertile ground for metastasis

In addition to its effect on platelets, the CNIO team found that a high-fat diet increases the expression of the protein fibronectin in lung tissue where tumor cells metastasize.

Fibronectin forms the tissue that connects lung cells, thereby helping to create a pre-metastatic niche into which the tumor cell enters. It also allows the tumor cell to interact more effectively with platelets. The scientists verified that the interaction of the tumor cell with both the lung endothelium and platelets is regulated by fibronectin.

To investigate the implications of these findings for patients, researchers from the CNIO Breast Cancer Clinical Research Unit, led by Miguel Ángel Quintela, participated in the study.

After analyzing blood samples from triple-negative breast cancer patients obtained before surgery and after undergoing chemotherapy, they were able to confirm that patients with higher blood clotting – shorter prothrombin time – were found to have a higher risk of recurrence within five years.

These findings “may help identify additional risk factors in breast cancer patients undergoing treatment, which will contribute to better clinical management of the disease,” the researchers said.

Potential clinical applications

The work, carried out in collaboration with other CNIO units and other centers in Spain and Canada, explored the first possibilities for clinical applications of the findings. One of them was to modify the diet in animal models. When the high-fat diet was abandoned and the mice lost weight, platelet counts and blood clotting returned to normal levels. As a result, metastasis decreased.

These results, combined with clinical studies from other groups, suggest a future in which dietary intervention or dietary modification, along with control of platelet activity, may improve the effectiveness of some anticancer therapies. This will not become a stand-alone treatment but may complement other treatments.

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Published: 03.04.2025

Updated: 02.04.2025

Medical author, Medical editor:

Stepan Yuk

Medical expert:

PhD. Olexandr Voznyak