Prevention of Radiation-Induced Breast Cancer by Amifostine

摘要

This project is a pre-clinical study designed to determine if amifostine might be effective in preventing breast cancer initiation by medical exposures to ionizing radiation. The experiments will determine if amifostine is protective in a murine model of breast cancer and, if so, determine the optimum dose, route and timing for its administration. The first year's objective was to test a high dose of amifostine administered I.P. prior to irradiation for reduction of ductal dysplasia in an outgrowth assay. Between September 2002 and May 2003, twenty-two donor mice were irradiated and 412 mammary fat pads were transplanted with mammary epithelial cells from these irradiated donors. Of these, 306 were harvested and examined as whole mounts. No dysplasias were seen, but due to the low outgrowth frequency no conclusions could be drawn on the effectiveness of amifostine. In August 2003 the PI changed institutions and experienced a delay of nearly 2 years in having the grant transferred. The project resumed in August 2005 with the establishment of a new breeding colony. An additional 116 mice were transplanted (232 fat pads) and outgrowths prepared for histology. Once again, there were few outgrowths and it was decided to switch from ductal dysplasia to frank mammary tumors as the experimental endpoint. A new Statement of Work was submitted in January 2007 and approved mid-April 2007. 294 mice divided into three groups: irradiated, irradiated and amifostine treated and unirradiated, were set up on June 1, 2007 and are being followed for mammary tumor development. At the time of this report there is no difference in survival between the groups. Histopathological classification of tumors is in progress.