The ideal strategy for controlling and reducing the social impact of disease is effective prevention. Individuals who are genetically predisposed to developing breast cancer have the opportunity to lower their risk through established preventative strategies, such as a mastectomy. While one of the most effective options, mastectomies have considerable short- and long-term impacts that reduce quality of life of the patient, especially for young women. To date, there are no risk-reducing medications that are as effective as surgery. Antisense oligonucleotide therapy has been very successful in reversing the symptoms of degenerative disorders by altering gene splicing. This proposal will investigate whether antisense oligonucleotides can eliminate the impact of high-risk genetic variants by modifying the process of gene splicing. This study will lay the foundation for the development of novel risk-reducing therapies to prevent cancer in genetically predisposed individuals.