关键词：乳腺癌；遗传学；基因组学；肿瘤
摘 要：The overarching goal of this proposal is to use massively parallel sequencing to detect somatic genomic alterations in breast cancer tumor samples in order to identify genetic determinants of tumor behavior that may inform clinical decision-making. To date, we have developed a targeted sequencing platform that interrogates approximately 450 genes that are known to be altered in breast cancer and other cancers. We now plan to utilize this platform to study 150 tumor samples from women with ER+ breast cancer who have had early-, late- or no relapse following endocrine therapy. We have also begun to sequence tumor samples from patients with advanced breast cancer. To date, we have performed whole exome sequencing on 8 patients. In 4 patients, we identified somatic genomic alterations with potential clinical impact. In 5 of the 8 patients, we also obtained and sequenced tumor samples at the time of resistance to targeted therapies. In some cases, known mechanisms of resistance (i.e., ligand-binding domain mutations in ESR1) were identified. Analysis is currently underway to further elucidate causes of resistance in those cases where the mechanism is unclear.