Obesity May Influence How Breast Cancer Becomes Invasive

OKLAHOMA CITY – 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 a known risk factor for invasive breast cancer, but researchers have not fully understood how it helps early, noninvasive breast lesions become invasive cancer. These findings could help improve physicians’ ability to predict and treat the disease.

In the study, breast cancers in women without obesity showed the typical signs of becoming invasive, including rapid cell division and increased ability to invade nearby tissue. But in women with obesity, researchers found 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 tumor. The tumor 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.”

Researchers also identified differences in the “neighborhood” of cells and tissues surrounding the cancer. Epithelial cells, where the tumor originally develops, co-opt other cells around them to create an environment 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 research team also discovered higher levels of an enzyme called Sulfatase 2 (SULF2) in tumor cells of women with obesity, suggesting that it may play an important role in cancer progression. SULF2 will be another focus of future studies.

Understanding what causes early, noninvasive tumors (ductal carcinoma in situ, or DCIS) to become invasive is important because not all women will develop invasive cancer, yet they 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.

“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.”

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About the project

The study, “Spatially Resolved Obesity-Driven Molecular Changes in Early Breast Cancer,” can be found at https://doi.org/10.1016/j.ajpath.2026.03.016. Samples for the study came from patients treated at the OU Health Stephenson Cancer Center, which funded the study, along with the OU Health Harold Hamm Diabetes Center. National Institutes of Health-funded resources were also used in the research. In addition to the scientists, the interdisciplinary research team included a breast cancer oncologist, a surgical oncologist, a pathologist, computational scientists, surgical medical residents and graduate students.

About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. In Oklahoma City, the OU Health Campus is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. The OU Health Campus serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about the OU Health Campus, visit www.ouhsc.edu.