Mayo Clinic Breast Cancer SPORE

项目概要/摘要 马约诊所乳腺癌孢子的第二次更新申请正在提交的愿景 乳腺癌的负担可以通过创新的转化研究来减轻 解决对妇女具有重要意义的问题。科学的孢子包括四个翻译 研究项目。项目1：“乳腺癌易感基因突变的癌症风险”， 非BRCA 1/BRCA 2基因包括在“基于面板”的测试。使用PROMPT登记，研究者将 定义与失活突变相关的乳腺癌的发病率， 不确定意义的变体和这些突变的病理“表型”。项目2：“治疗性 三阴性乳腺癌（TNBC）中ERβ的靶向作用”是基于马约研究者的数据，当ERβ 在TNBC中表达，是预后性的，并且ERβ激动剂通过TGFβ途径抑制增殖。 该项目的高潮是在转化性乳腺癌中ERβ+TNBC中雌二醇的II期研究。 研讨会。项目3：“以麻疹病毒为基础的免疫病毒疗法治疗转移性 乳腺癌”是基于马约研究人员开发麻疹病毒（MV）的开创性工作， 免疫刺激转基因（MV-NAP），以及MV-NAP与PD-1阻断剂的协同抗肿瘤活性。 该项目包括MV-NAP I期研究，以及开发其他临床前数据， MV-NAP和PD-1阻断剂联合应用的临床试验。项目4：“ 芳香化酶抑制剂（AI）在早期绝经后乳腺癌中的作用”是基于 雌激素水平在AI治疗的妇女。研究人员计划对辅助AI试验进行二次分析， 确定雌激素抑制不足是否与癌症复发有关，然后进行 全基因组分析，以确定与“最佳”雌激素阈值相关的遗传变异， 临床研究中的前瞻性验证。这些研究项目由三个高度互动的 核心：核心A：管理核心，核心B：生物标本和病理学核心，核心C：生物统计学， 生物信息学和患者注册中心。发展研究计划将继续确定和 开发研究项目，最有希望推进到完整的SPORE项目，以及职业生涯 增强计划将继续确定和支持教师研究人员在乳腺癌转化 最有潜力成为未来SPORE领导者的研究。研究人员，核心，和 SPORE的研究项目都整合在马约诊所癌症中心。总的来说，我们的孢子 将做出发现并将其转化为诊所，以造福于患有乳腺癌或有乳腺癌风险的妇女。 癌

Program Summary/Abstract This second renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with the vision that the burden of breast cancer can be reduced through the performance of innovative translational research addressing issues of high significance for women. The science of the SPORE includes four translational research projects. Project 1: “Cancer risks for mutations in breast cancer predisposition genes” focuses on non-BRCA1/BRCA2 genes included in “panel based” tests. Using the PROMPT registry, the investigators will define the penetrance of breast cancers associated with inactivating mutations, the clinical relevance of variants of uncertain significance, and pathological “phenotype” of these mutations. Project 2: “Therapeutic targeting of ERβ in triple negative breast cancer (TNBC)” is based on Mayo investigator data that ERβ, when expressed in TNBC, is prognostic, and that ERβ agonists suppress proliferation through the TGFβ pathway. This project culminates in a phase II study of estradiol in ERβ+TNBC within the Translational Breast Cancer Research Symposium. Project 3: “Measles virus based immunovirotherapy in the treatment of metastatic breast cancer” is based on pioneering work of Mayo investigators to develop a measles virus (MV) that expresses an immunostimulatory transgene (MV-NAP), and the synergistic antitumor activity of MV-NAP with PD-1 blockade. This project includes a MV-NAP phase I study, and development of additional preclinical data that will inform the clinical trial of the combination of MV-NAP and PD-1 blockade. Project 4: “Pharmacogenomics of aromatase inhibitors (AI) in early stage postmenopausal breast cancer” is based upon the importance of estrogen levels in AI-treated women. The investigators plan secondary analyses of adjuvant AI trials to determine whether inadequate estrogen suppression is associated with cancer recurrence, followed by a genome-wide analysis to identify genetic variants associated with the “optimal” estrogen threshold and then prospective validation in a clinical study. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B: Biospecimen and Pathology Core, and Core C: Biostatistics, Bioinformatics, and Patient Registry Core. A Developmental Research Program will continue to identify and develop research projects that hold the greatest promise to advance to full SPORE projects, and a Career Enhancement Program will continue to identify and support faculty investigators in breast cancer translational research that have the greatest potential to become future SPORE leaders. The investigators, cores, and the research programs in the SPORE are all integrated in the Mayo Clinic Cancer Center. Collectively, our SPORE will make discoveries and translate them into the clinic for the benefit of women with, or at risk of breast cancer.