Breast Oncology Program: Summary/Abstract The goal of the HDFCCC Breast Oncology (BR) Program is to reduce the risk of breast cancer development, progression, and mortality using innovative approaches and novel methodologies to reveal the molecular, cellular, and targetable networks that underlie susceptibility, heterogeneity, and outcome disparities. The translational nature of the program means that laboratory-based work in the program can be rapidly moved into clinical trials. The clinical research of the BR Program includes reducing overdiagnosis, over- and under- treatment, and the burden of cancer therapy through risk assessment to individualize screening and prevention measures, and through improved tumor classification to tailor treatment. BR research focuses on three areas: (1) understanding how tumor heterogeneity contributes to metastasis, dormancy, and therapeutic resistance; (2) developing new therapeutic strategies using innovation in trial design and drug development; and (3) better characterizing early breast lesions to improve screening, prevention, and health care value.