Mayo Clinic Breast Cancer SPORE

计划摘要/摘要 梅奥诊所乳腺癌孢子的第二次续签申请正在与VISION一起提交 通过创新的转化研究可以减轻乳腺癌的负担 解决对妇女具有高度重要性的问题。孢子学包括四个翻译 研究项目。项目1：“乳腺癌易感基因突变的致癌风险”侧重于 非BRCA1/BRCA2基因包括在“基于小组”的测试中。使用即时登记，调查人员将 定义与失活突变相关的乳腺癌的外显性，临床相关性 不确定意义的变异，以及这些突变的病理“表型”。项目2：“治疗学” 三阴性乳腺癌的ERβ靶点“是基于梅奥调查者的数据，ERβ，当 ERβ激动剂通过转化生长因子β途径抑制细胞增殖。 该项目最终在转化性乳腺癌ERβ中雌二醇的第二阶段研究中达到高潮。 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肿瘤 乳腺癌“是基于梅奥研究人员的开创性工作，开发出一种能够表达 免疫刺激转基因(MV-NAP)及MV-NAP与PD-1拮抗剂的协同抗肿瘤活性。 该项目包括MV-NAP第一阶段研究，以及其他临床前数据的开发，这些数据将为 MV-NAP联合PD-1阻滞剂的临床研究项目4：“药物基因组学” 芳香酶抑制物(AI)在绝经后早期乳腺癌中的应用“是基于 接受人工智能治疗的女性的雌激素水平。研究人员计划对人工智能佐剂试验进行二次分析，以 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，然后 临床研究中的前瞻性验证。这些研究项目得到了三个高度互动的项目的支持 核心：核心A：行政核心，核心B：生物质学和病理学核心，核心C：生物统计学， 生物信息学和患者登记核心。发展研究计划将继续确定和 开发最有希望发展到全孢子项目的研究项目，并在职业生涯中 增强计划将继续识别和支持乳腺癌翻译学院的研究人员 最有可能成为未来孢子领袖的研究。调查人员、核心和 孢子中的研究项目都整合在梅奥诊所癌症中心。总而言之，我们的孢子 将做出发现，并将其转化为临床，以造福于患有乳房或有乳房风险的女性 癌症。

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.