Women with breast cancer arising as a consequence of germline mutations in BRCAl or BRCA2 are known to be at significant risk of contralateral breast cancer (CBC) . Our group has reported that approximately 25% of Ashkenazi women undergoing breast conserving treatment for hereditary breast cancer develop CBC within 10 years. Examination of factors influencing contralateral risk will provide insight into prevention strategies for unaffected women with BRCA mutations at risk for hereditary breast cancer. To evaluate these factors, the funded study is evaluating the impact of tamoxifen and radiotherapy on CEC risk. In this reporting period, the human subjects protocol was developed and approved by the local IRS and the relevant DOD authority. Tamoxifen treatment data were acquired and analyzed for the 305 women in the original 1980-1990 dataset. Mutation carriers taking tamoxifen were found to have a non-significant reduction in contralateral risk (0.57 95% CI: 0.07-4.57; p=0.6) . These data will be presented at the 2002 Era of Hope meeting. Dataset expansion continues per the SOW. 422 additional Ashkenazi women with invasive breast cancer (1990-1992)and available tissue have been identified, and clinical data collection is underway. Further cases are being identified in the 1992-1994 time period.