Study could explain why obesity is a breast cancer risk factor

Obesity may reduce a fat-cell process that helps kill breast cancer cells, offering a possible explanation for its link to the disease, a study found.

The findings come from preclinical models, including breast tissue from donors.

The research team at Huntsman Cancer Institute at the University of Utah focused on adipocytes, the fat cells that make up much of breast tissue.

Adipocytes are larger in obesity than in lean tissue and create different environments around cancer cells.

Researchers found that lean adipocytes produced much more of a fatty acid called 9S-HODE than obese adipocytes.

9S-HODE promotes ferroptosis, a form of cell death that helps the body remove old and damaged cells, including cells that could be cancerous.

Cancerous cells died more readily in lean tissue, where levels of 9S-HODE were higher.

Meghan Curtin, first author and a doctoral candidate in molecular biology, said: “We found that the lean adipocytes produce much more 9S-HODE than obese ones. This means that cancerous cells die more readily in lean tissue.

“By producing more 9S-HODE, our bodies are actively protecting us, under lean circumstances, in a way it cannot with obesity.”

In preclinical mouse models, increasing levels of 9S-HODE in obese adipocytes suppressed breast cancer tumour growth.

The researchers believe this understanding could lead to better therapies.

Keren Hilgendorf, senior author of the study and an investigator at Huntsman Cancer Institute, said: “From a clinical perspective, this discovery is incredibly empowering. Because 9S-HODE is naturally present in the body but is lost with obesity, we may be able to restore this protection by putting it back.”

“That could become a very feasible therapeutic approach to slow breast cancer growth.

The researchers stressed that obesity is only one factor that contributes to breast cancer and that the disease can develop for other reasons.

They also said 9S-HODE appears to be produced mainly by fat cells in the breast, although fat cells elsewhere in the body may have a similar protective function that requires further research.