By Jill Pease
The National Cancer Institute’s Epidemiology and Genomics Research Program has added a study led by Lusine Yaghjyan, M.D., Ph.D., M.P.H., an associate professor in the Department of Epidemiology at the University of Florida College of Public Health and Health Professions, to its list of 2025 Research Highlights. The study provides new insights into the role of age-related changes to breast tissue in the development of breast cancer.
Each year, the Epidemiology and Genomics Research Program showcases a selection of research publications authored by scientists who receive grants from the organization. This is the second consecutive year Yaghjyan’s research has been recognized among the program’s Research Highlights.
Yaghjyan conducted the study with colleagues at Harvard Medical School and Weil Cornell Medicine. Their paper, which appeared in the journal Cancer Epidemiology, Biomarkers & Prevention, examined terminal duct lobular unit, or TDLU, involution, which has previously been linked to breast cancer risk.
TDLUs are structures within the breast that produce milk during lactation. With age, TDLUs undergo changes, a process known as involution. A lower degree of TDLU involution may increase the risk of breast cancer. The study by Yaghjyan and colleagues is the first to examine associations of breast stem cell markers with TDLU involution in cancer-free women.
“TDLUs are where breast cancer originates, and changes in normal TDLUs may represent early stages of breast cancer development,” said Yaghjyan, a member of the UF Health Cancer Institute. “Understanding these molecular changes may lead to novel prevention strategies targeting early stages of breast carcinogenesis.”
Investigators examined data from more than 300 cancer-free women with benign breast biopsies who were enrolled in the Nurses’ Health Study, a long-term investigation of chronic disease risk factors in women. The team found that two of three breast stem cell markers were associated with lower degree of TDLU involution, which is associated with increased breast cancer risk.
“The most exciting aspect is that the findings are in line with the stem cell hypothesis of breast carcinogenesis,” Yaghjyan said. “According to this hypothesis, the number and activity of normal stem cells in the breast tissue may explain the risk of breast cancer. The current study is one of a few we have done within this grant that now provide the first epidemiological evidence on stem cell contributions to early stages of breast cancer development.”
Yaghjyan and her team are currently conducting other analyses to better understand the relationship of other breast cancer risk factors with stem cell marker expression. They also plan to expand the number of stem cell markers under examination.
“As stem cell activity could be modified by targeted therapies, we hope that our results, once confirmed, could lay the groundwork for development of stem cell-directed breast cancer prevention strategies,” Yaghjyan said.