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.”