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Obesity Linked to Distinct Biological Changes in Early-Stage Breast Cancer Progression

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Obesity May Alter How Early-Stage Breast Cancer Becomes Invasive

A study by University of Oklahoma researchers, published in The American Journal of Pathology, has uncovered how obesity may change the mechanism by which early-stage breast cancer progresses to an invasive form.

Key Findings

"This could be why women with obesity are at higher risk for invasive breast cancer. The changes that the cancer cells are undergoing are allowing them to survive and thrive."
— Bethany Hannafon, Ph.D., co-lead author

In women without obesity, invasive progression showed typical signs: rapid cell division and increased invasive capacity.

In women with obesity, researchers observed a markedly different set of changes:

  • Increased inflammation in the tumor environment, driven by immune cells that actively promoted tumor growth.
  • Enhanced survival of tumor cells under stress.
  • Changes in cellular metabolism, altering how cancer cells use nutrients for energy.

The Microenvironment Makes a Difference

Researchers also found significant differences in the surrounding tissue, known as the microenvironment. Epithelial cells co-opted other cell types to create a more cancer-conducive environment.

Additionally, higher levels of the enzyme Sulfatase 2 (SULF2) were found in tumor cells of women with obesity, suggesting a potential role in cancer progression.

"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. That may be an area of future study."
— Elizabeth Wellberg, Ph.D., co-lead author

Background

Obesity is a known risk factor for invasive breast cancer, but the underlying mechanisms were not fully understood until now.

Ductal carcinoma in situ (DCIS)—a noninvasive tumor—becomes invasive in about half of diagnosed women. Currently, there is no way to determine which women are at highest risk, leading to widespread overtreatment.

A Growing Concern

"Obesity is on the rise – 50% of Americans are expected to be obese by 2030. That statistic further highlights the importance of considering a patient's metabolic health alongside the biology of the tumor itself."
— Cole Hladik, Ph.D., first author

Implications

The findings may help improve prediction and treatment of breast cancer progression, potentially reducing overtreatment in women with DCIS who are at low risk.