Lymphedema is a dreaded complication of primary breast cancer therapy with the capacity to degrade quality of life. Breast cancer patients who develop lymphedema are more likely to become depressed, anxious, sexually dysfunctional and unemployed. Lymphedema cannot be cured. Current treatment strategies attempt to control swelling largely through the use of compressive garments and wrapping. While lymphedema treatment may succeed, it is costly, time-consuming, and aggravates patients¿ perceptions of disfigurement and reduced quality of life. Novel means are needed to prevent lymphedema and spare patients the associated long-term social, psychological, and economic burden.

Surgical dissection of lymph nodes, an essential component of breast cancer staging and treatment, was historically held to be the primary cause of breast cancer-related lymphedema. However, many patients undergo extensive lymph node resections and fail to develop lymphedema, or develop lymphedema months after their surgery. It is now recognized that the lymphatic system restores arm drainage by establishing alternate lymphatic pathways. These collateral pathways frequently provide adequate arm drainage but may be damaged by radiation therapy. Radiation is an integral component of most primary breast cancer therapy. Considerable evidence has accrued implicating radiation therapy in the development of lymphedema. Higher radiation doses delivered to larger areas increase the likelihood that a patient will develop severe lymphedema. Most lymphedema develops 6-12 months after completion of radiation therapy. This time frame corresponds to the expected onset of radiation toxicity. Additionally, treatments that minimize radiation toxicity reduce breast edema. Little effort has been yet been devoted to exploring strategies for minimizing radiation-induced injury to the lymphatic system.

The proposed study will use lymphoscintigraphy to: (1) characterize changes in lymph drainage patterns that develop after irradiation of lymph nodes and vessels, and (2) determine whether irradiation of critical lymphatic structures is associated with decreased upper extremity lymph drainage and increased arm size. This study will follow a group of 50 breast cancer patients with positive lymph nodes during and after their radiation therapy. Lymphoscintigraphy will be performed before radiation therapy and 12 months after the initiation of radiation. At each time point, patients will be asked to fill out a questionnaire inquiring whether they have developed signs or symptoms of lymphedema, and their arms will be measured. By comparing the lymphatic function and arm size of patients who receive radiation to critical drainage pathways to those who do not, we will quantify the degree to which radiation contributes to the development of lymphedema. This investigation will establish a foundation for future trials of radiation therapy techniques designed to preserve lymphatic function.

This study will realized the goals of the Breast Cancer Research Program by exploring a novel means of refining conventional radiation therapy to reduce patients risk of developing a devastating and long-term complication, lymphedema.