Uncovering mechanisms responsible for shoulder morbidity following radiotherapy

As advances in treatment seek to end breast cancer, a new focus is needed on the functional abilities of those who benefit from these treatments to ensure that breast cancer survivors can maintain a high quality of life. The inclusion of radiotherapy in breast cancer treatment has successfully improved survival rates of patients diagnosed with early-stage breast cancer. Yet these same patients can experience shoulder disease in the months and years after radiotherapy, including pain, weakness, and restricted movement. These limitations affect a patient’s daily living, including their ability to lift and carry objects or maintain employment. There is a poor understanding of why shoulder disease develops following radiotherapy, which has prevented the development of appropriate interventions that can eliminate shoulder complications due to radiotherapy. Therefore, the objective of this proposal is to determine the time progression and physiological causes of shoulder disease in breast cancer patients. We suspect that the build-up of scar tissue in the skin, fat, and muscle tissues exposed to radiation can predispose some breast cancer patients to shoulder disease. Since multiple muscles control the shoulder, scar tissue from radiation in one or more muscles may alter a patient’s ability to use their affected shoulder. However, current clinical methods cannot detect shoulder disease until the patient is severely affected. Furthermore, they cannot isolate the cause of shoulder disease in breast cancer patients. In this proposal, we will introduce new clinical methods that can robustly assess shoulder stiffness, which is a quantitative measure of the shoulder’s functional capacity to move and generate force. These shoulder stiffness measurements will be directly compared to ultrasound images of the muscles exposed to radiation, which can help identify if radiation-induced scar tissue precedes shoulder disease following radiotherapy. Our specific aims are 1) to determine the longitudinal effect of radiotherapy on shoulder stiffness and 2) to quantify the physiological causes contributing to shoulder stiffness. We will investigate these specific aims in 20 women undergoing radiotherapy of the breast and 20 women undergoing radiotherapy of the breast and draining lymphatics. The inclusion of different treatment plans will allow us to determine if increasing the area exposed to radiation produces worse shoulder outcomes. Patients in both aims will be examined at four time points during their first year of recovery. The proposed research will assist in the prevention, screening, and rehabilitation of women undergoing radiotherapy, including using the clinical tools developed here to adjust radiotherapy treatments to maximize disease free survival and shoulder function. The applicant will gain key training in radiation oncology to help translate these tools and insights to improved patient outcomes in their own independent laboratory.