Assessing the impact of early physiotherapy on lymphatic dysfunction in breast cancer survivorship - Project Summary Breast cancer related lymphedema (BCRL) is a chronic, incurable condition that negatively impacts quality of life due to abnormal swelling causing arm/chest tightness, heaviness, pain, and impaired limb function. BCRL is typically diagnosed by a 5-10% increase in relative arm volume after irreversible fluid accumulation and tissue swelling occurs. Complete decongestive therapy, consisting of a regimen of manual lymphatic drainage, compression bandaging, and skin care forms the basis of lymphedema treatment and has largely remained unchanged for decades. Intervention at first diagnosis, based on limb volume, with continued patient compliance results in better outcomes for patients but is not curative. Recent studies using near-infrared fluorescence lymphatic imaging (NIRF-LI) indicate that lymphatic dysfunction, in the form of dermal backflow, can be screened on average, approximately eight months prior to conventional clinical BCRL diagnosis, based on limb volume. Importantly, lymphatic dysfunction was reduced after just two weeks of daily physical rehabilitation in 75% of patients recently diagnosed with early head and neck cancer-related lymphedema. We hypothesize that early physical rehabilitation with advanced pneumatic compression, provided at the first sign of lymphatic dysfunction and before the onset of BCRL, may resolve lymphatic dysfunction. This will prevent the development of lymphedema and enhance the quality of life in breast cancer survivors. Our specific aims are, (1) Longitudinally assess lymphatic dysfunction in breast cancer survivorship using 3D qNIRF-L, (2) Assess impact of early physical rehabilitation on lymphatic dysfunction in cancer survivorship, (3) Assess the durability of lymphatic response to early physical rehabilitation. We expect that early physical rehabilitation will decrease or ameliorate lymphatic dysfunction reducing the incidence of lymphedema and that these changes will be durable and curative, with permanent restoration of lymphatic function. The collaborations include MPIs at M.D. Anderson Cancer Center, which treats advanced breast cancer patients at highest risk for lymphedema, and at UTHealth, where translation of NIRF-LI originated, as well as collaboration with the University of Houston for data analytics. If successful, the clinical trial conducted in this project will provide objective criteria for early deployment of physical rehabilitation to prevent cancer-acquired lymphedema before its irreversible onset, improving the quality of life of cancer survivors while demonstrating a simple, point-of-care strategy for archival documentation of subclinical lymphatic dysfunction.