P16 expression is a major biomarker of aging and a measure of organ reserve. The p16 gene codes for an intracellular protein which in humans, increases 10 to 20 fold between the ages of 20 and 80 years. This protein blocks cell division in almost all organs and results in cellular aging. Cells with high p16 expression are less capable of dividing than cells with low expression. Patients with higher levels of cellular p16 protein in their bone marrow stem cells, and cells lining the mouth, esophagus, and stomach, could have greater toxicity with chemotherapy since after treatment these cells would take longer to replicate as compared to patients with lower p16 levels. Dr. Muss and colleagues have now completed patient entry to a trial to determine if p16 is an independent predictor of chemotherapy toxicity, and data analysis is underway. They have also convincingly shown that common chemotherapy regimens used for the adjuvant treatment of breast cancer result in a one- to two-fold rapid increase in p16 expression in circulating immune cells (T-lymphocytes) in the blood (a manuscript is under review). In addition, Dr. Muss's preliminary data suggests that patients with a greater change in p16 levels during chemotherapy are more likely to have greater hematologic toxicity – supporting their hypothesis that p16 expression may prove to be an independent predictor of chemotherapy-related side-effects. In laboratory models high levels of p16 are associated with shortened survival, and Dr. Muss's team now plans to expand their study of p16 to test a scalable exercise program (walking and strength training) as a means to reduce the rate of p16 change in patients receiving adjuvant chemotherapy for breast cancer. If so, this may have major implications for long term survival in this potentially curable group of women.
Dr. Muss’ team has shown that a walking program in women on aromatase inhibitors was feasible and well received (Nyrop et al, J Geriatric Oncol, in press). They are now analyzing data from an ongoing trial testing the feasibility of a walking program during chemotherapy in older women and are now about to open another trial to test this same walking program in younger women. If a simple scalable intervention like walking can reduce the rate of p16 change in patients receiving adjuvant chemotherapy for breast cancer, it would have major implications for improving function and long term survival in this curable group of women.
Dr. Muss is currently Professor of Medicine at the University of North Carolina, Chapel Hill and Director of Geriatric Oncology at the Lineberger Comprehensive Cancer Center. His major research interests are breast cancer, with emphasis on the treatment of older women, issues related to treatment of all older cancer patients, and providing education in geriatrics to fellows in training. With his colleagues, Dr. Muss is trying to define to role molecular factors as well as geriatric assessment in optimizing treatments for older patients with cancer.
Dr. Muss is currently Co-Chair of the Cancer in the Elderly Committee for the Cancer and Leukemia Group B (CALGB), a National Cancer Institute sponsored cooperative group which endeavors to increase awareness and clinical trials opportunities for older patients. Partly through his efforts, the CALGB was awarded and completed major study on the use of adjuvant chemotherapy in older women with high risk/early stage breast cancer. Dr. Muss is a prior member of the Board of Directors of the American Society of Clinical Oncology (ASCO), the ASCO Foundation, and chairs their task force on Geriatric Oncology. He has previously served as Chair of the Medical Oncology Board for the American Board of Internal Medicine.