An association between a key cellular pathway and connective tissue in the breast could ultimately lead to new strategies to prevent breast cancer early on, UF Health Cancer Institute researchers and collaborators have found.
The breast contains tissue called stroma that’s responsible for several major functions, including how cells multiply and communicate with each other.
At the same time, a cellular pathway called the insulin-like growth factor (IGF) pathway regulates cell differentiation, natural cell death and some aspects of non-cellular parts of breast tissue. In normal breast tissue of cancer-free women, it was unknown whether this pathway impacts cells in the stroma called fibroblasts. In breast tumors, cancerous fibroblasts have been associated with more aggressive cancers and resistance to treatment.
“For the first time, we looked at associations between the IGF pathway and the expression of breast stromal markers related to fibroblasts,” said Lusine Yaghjyan, M.D., Ph.D., an associate professor in the Department of Epidemiology in the UF College of Public Health and Health Professions and first author of the new study, presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego.
Along with collaborators at Weill Cornell Medicine, Yaghjyan used data and samples from 145 cancer-free women with benign breast biopsies who were participants in the Nurses’ Health Study II.
“It was important that we were looking at cancer-free women so that the results were not influenced by any changes after cancer develops,” Yaghjyan said. “Our goal was to see what was happening very early in the process of cancer development.”
The team found an association between two IGF pathway markers and stromal markers, while accounting for other risk factors known to influence the pathway or breast cancer risk overall.
“This is the first epidemiological evidence from human studies in cancer-free women to show a suggestive relationship, which was in line with what you would expect to see based on past research about the links between the IGF pathway and breast cancer risk,” Yaghjyan said. “Our findings add to our knowledge of how the IGF pathway might be contributing to tumor development in the early stages.”
If confirmed in further studies, the findings could be used to identify women who might be at greater risk of stromal changes that could increase their breast cancer risk. Women with high levels of IGF proteins could be then considered for cancer prevention with stroma-directed therapies.
The researchers plan to further study the relationship using different techniques.
