Abstract : The estrogen receptor (ER) plays a major role in breast tumor progression, we have recently discovered a somatic mutation (A908G) that leads to a lysine to arginine (K303R) amino acid change. Here we proposed to study if the K303R ER mutation is prognostic clinical factor for invasive breast cancer. Our initial studies have indicated that the mutation is present in approximately 53% of invasive breast cancers. Additionally, the mutation was more prevalent in nodepositive breast cancer versus node-negative breast cancer (85% vs. 38%, respectively). Specific Aim 1 has been completed and we are proceeding with specific Aim 2. Analyzing a larger patient population with long-term clinical follow-up. In the near future we will be begin creating the expression vectors and cell lines required to complete specific Aim 3. While our initial data suggest that the K303R ER mutation may be involved in tumor progression and metastasis, completion of specific Aims 2 and 3 will confirm these results.