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INTEGRATIVE GENOMIC ANALYSIS OF MEDIATORS OF BREAST CANCER SURVIVAL Shannon Bailey, PhD Center for Functional Cancer Epigenetics Department of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School Breast cancers employ various mechanisms to facilitate their survival and growth. Consequently, there are a number of breast cancer subtypes, and each may require differe nt therapeutic approaches. The estrogen receptor (ER) is an estrogen-regulated transcription factor that controls the transcription of numerous genes and noncoding RNAs, and it is a key target for therapy in ER-positive breast cancers. For over 40 years, this molecule has served as the primary determinant for identifying patients for treatment with endocrine therapy. While this treatment has proven to be effective, many patients ultimately develop therapeutic resistance. Thus, new treatment modalities are needed to improve outcome. In addition, new methods and biomarkers for identifying patients who will or will not respond to particular treatments are also needed to determine refined patient subsets for better management of this disease. In the first part of this talk, I will describe our efforts to better characterize chemoendocrine resistant breast cancers by exploring the interplay between downstream targets of ER and the tumor suppressor p53. This is a study that has identified a new treatment paradigm for patients with ER-positive breast cancer. The second part of the talk will center on a study in which ERregulated microRNAs were examined by NanoString technology to determine their role in different breast cancer subsets. This is a study in which we found that a specific cluster of microRNAs is directly regulated by ER and acts as a biomarker for a poor-surviving patient subset. Both studies take advantage of integrative genomic analyses involving the use of biological assays, next-generation technologies, ‘big data’ analysis of patient samples, and cistromic studies.