Titles and Affiliations
Director, Leonard P. Zakim Center for Integrative Therapies and Healthy Living
Associate Professor, Medical Oncology
Research area
Investigating the link between exercise, irisin, and breast cancer development.
Impact
Higher levels of physical activity have been linked to lower risk of developing breast cancer, with studies showing that women who exercise regularly have an approximately 20% lower risk of developing breast cancer compared with women who do not exercise, a reduction seen in both older and younger women and across all breast cancer subtypes. Despite this evidence, the processes by which exercise could impact breast cancer are not well understood. Exercise has been shown to activate the immune system in breast cancers and in non-cancerous breast tissue. Dr. Ligibel has demonstrated that irisin, a hormone released by muscle during exercise, slows breast cancer development potentially through immune system activation. Dr. Ligibel’s research aims to integrate evidence connecting exercise, irisin, and breast cancer development to better understand the pathways through which exercise could lower disease risk.
Progress Thus Far
Dr. Ligibel and her team conducted a comprehensive investigation of the impact of irisin on the immune landscape in a “high-risk” breast cancer model. They found that irisin exerts its main effects on cancer by activating the immune system in the tissue surrounding the tumor, rather than impacting the tumor itself. Their prior work in women with newly diagnosed breast cancer also found that exercise leads to increased expression of immune markers in malignant breast tissue. In conjunction with the laboratory studies, Dr. Ligibel is enrolling women with dense breasts to a clinical trial (NCT06322888) that evaluates the impact of exercise on levels of circulating irisin, as well as immune markers in non-cancerous breast tissue. The study enrolls women who are not exercising regularly and who have dense breasts on mammogram, which is linked to an increased risk of breast cancer. The clinical trial is open to enrollment, with 27 of a planned 46 participants currently enrolled. Uptake of the exercise program has been strong, with participants completing more than 90 percent of prescribed exercise sessions. These projects will help to determine the mechanisms through which exercise could reduce breast cancer risk, as well as to identify new targets for the development of drugs that could prevent breast cancer.
What’s next
Building on this work, Dr. Ligibel’s team will examine the impact of exercise on breast tissue before cancer forms. They will compare immune marker expression in non-cancerous breast tissue samples from women assigned to a 12-week exercise program compared to those assigned to a control group, leveraging biopsy samples collected as part of the team’s BCRF Precision Prevention Initiative project. The team will focus on T cell and myeloid lineage markers and overall immune composition, and will correlate these findings with circulating irisin levels to build one of the most comprehensive datasets to date on the mechanisms linking exercise to breast cancer risk.
Biography
Jennifer Ligibel, MD is the director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living and is an associate professor of medical oncology at the Dana-Farber Cancer Institute. She completed her medical degree at Washington University in St. Louis, followed by a residency in internal medicine at Massachusetts General Hospital and fellowship in medical oncology at Dana-Farber Cancer Institute/Partners Cancer Care in Boston, Massachusetts. Dr. Ligibel’s currently serves as the Chair of the American Society of Clinical Oncology Cancer Care Delivery Council and the Prevention Committee Vice Chair of the Alliance for Clinical Trials in Oncology. Her research is focused on the impact of energy balance factors, such as physical activity and body weight, upon cancer risk and outcomes. Her long-term goals are to evaluate the impact of energy balance interventions, including weight loss and increased physical activity, on cancer recurrence and survival, and to determine the best methods of implementing these interventions in oncology practice.
