Mayo Clinic Breast Cancer SPORE

梅奥诊所乳腺癌孢子的续期申请正在梅奥诊所癌症中心（MCCC）和梅奥基金会的全力支持下提交，以继续进行旨在减少乳腺癌负担和死亡率的转化研究。SPORE科学包括四个转化性研究项目：项目1：“BRCA1和BRCA2乳腺癌易感性基因中不确定意义变异（VUS）携带者的风险评估”将继续这项具有临床重要性和高度转化性的研究，解决许多女性在进行BRCA1 /2测试并给予VUS结果时确定其个人乳腺癌风险的明确未满足需求。项目2：“Endoxifen作为一种新的乳腺癌激素疗法”是基于Mayo研究者得出的临床前数据，该数据表明Endoxifen比他莫昔芬具有更好的抗肿瘤活性。这些数据促使NCI开发临床级endoxifen，该药物将用于SPORE项目的首次人体I期临床试验。项目3：“IGF和胰岛素系统信号对激素抵抗乳腺癌的调节”通过关注胰岛素受体a异构体作为胰岛素生长因子通路信号传导的（共）介质的作用，重点关注一种处理激素治疗抵抗的新方法。计划进行更多的临床前研究，并将在II期临床试验中检查完整的IGF和雌激素受体阻断，该试验将以在联合领导实验室进行转化研究的密集生物标本采集（包括活组织检查）而着称。项目4：“改善乳腺良性疾病女性的乳腺癌风险预测”解决了利用患者乳腺良性组织（BBD）的特征更好地预测个体患者风险的高度重要需求。该项目将识别新的生物标志物，并使用大型Mayo BBD队列建立风险预测模型，随后在SPORE-SPORE合作中进行验证。这些研究项目由三个高度互动的核心支持：核心A：行政核心，核心B；生物标本和病理学核心，以及核心C：生物统计学和患者登记核心。一个发展研究项目将继续确定和发展最有希望推进完整的SPORE项目的研究项目，一个职业发展项目将继续确定和支持在乳腺癌转化研究中最有潜力成为未来SPORE领导者的教师研究人员。SPORE的研究人员、核心设施和研究项目都被整合到MCCC中，共同促进知识的发展，并将研究结果转化为临床研究，以造福患有乳腺癌或有患乳腺癌风险的妇女。

This renewal application of the Mayo Clinic Breast Cancer SPORE is being submitted with full support of Mayo Clinic Cancer Center (MCCC) and Mayo Foundation to continue translational research directed at reducing the burden and mortality from breast cancer. The science of the SPORE includes four translational research projects: Project 1: "Risk assessment for carriers of Variants of Uncertain Significance (VUS) in the BRCA1 and BRCA2 breast cancer predisposition genes" will continue this clinically important and highly translational research that addresses a clear unmet need of many woman to determine their personal risk of breast cancer when tested for BRCA 1/2 and given the result of a VUS. Project 2: "Endoxifen as a novel hormonal therapy for breast cancer" is based on Mayo investigator derived preclinical data indicating that endoxifen has superior anti-tumor activity than tamoxifen. These data led NCI to develop clinical grade endoxifen, which will be used in a first-in-human phase I clinical trial in this SPORE project. Project 3: "Regulation of hormone resistant breast cancer by IGF and insulin system signaling" focuses on a novel approach to dealing with resistance to hormonal therapy by focusing on the role of the insulin receptor A isoform as a (co-)mediator of insulin growth factor pathway signaling. Additional pre-clinical studies are planned and complete IGF and estrogen receptor blockade will be examined in a phase II clinical trial that is notable for intensive biospecimen acquisition, including biopsies, for translational studies in the Co-Leaders' labs. Project 4: "Improving breast cancer risk prediction for women with benign breast disease" addresses the highly important need for better prediction of risk in the individual patient utilizing features present in the patient's benign breast tissue (BBD). This project will identify novel biomarkers and build a risk prediction model using the large Mayo BBD Cohort with subsequent validation in a SPORE-SPORE collaboration. These research projects are supported by three highly interactive cores: Core A: Administrative Core, Core B;. Biospecimen and Pathology Core, and Core C: Biostatistics 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 Development 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, core facilities, and the research programs in the SPORE are all integrated into the MCCC and, collectively, will advance knowledge and translate findings into the clinic for the benefit of women with, or at risk for, breast cancer.