Whole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T).

611 Background: While 50-70% of pts with HER2+ MBC treated with T respond to therapy, the vast majority eventually develop resistance, after a median duration of 1 year. In rare cases, pts have exceptionally long durations of response to T. Understanding mechanisms of exceptional responses to anticancer therapies may improve patient selection and rational treatment designs. Methods: We conducted a retrospective screen for pts with HER2+ MBC at the Dana Farber Cancer Institute treated with T in the metastatic setting for more than 60 months. To date, we have identified 3 pts with extraordinary responses to T who provided consent for genomic studies and had sufficient tumor tissue available for study. All pts had histologic confirmation of metastatic disease and radiologic confirmation of response. Deep WES was performed on DNA extracted from pre-trastuzumab tumor biopsies and matched normal blood samples from all 3 pts, and sequencing data was analyzed for somatic point mutations, small insertions/deletion...