Mayo Clinic Breast Cancer SPORE

马约诊所乳腺癌孢子的更新申请是在马约诊所癌症中心（MCCC）和马约基金会的全力支持下提交的，以继续进行旨在降低乳腺癌负担和死亡率的转化研究。SPORE的科学包括四个转化研究项目：项目1：“BRCA 1和BRCA 2乳腺癌易感基因中不确定意义变异体（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，该研究解决了许多妇女在检测BRCA 1/2时确定其乳腺癌个人风险的明确未满足需求。2，并给出了一个VUS的结果。项目二：“Endoxifen作为乳腺癌的新型激素疗法”是基于马约研究者得出的临床前数据，表明endoxifen具有比他莫昔芬更上级的抗肿瘤活性。这些数据导致NCI开发临床级内昔芬，将用于该SPORE项目的首次人体I期临床试验。项目三：“通过IGF和胰岛素系统信号传导调节激素抵抗性乳腺癌”通过关注胰岛素受体A同种型作为胰岛素生长因子途径信号传导的（共）介体的作用，关注处理对激素治疗的抵抗的新方法。计划进行额外的临床前研究，并将在II期临床试验中检查IGF和雌激素受体的完全阻断，该临床试验以密集的生物标本采集（包括活检）而闻名，用于共同领导人实验室的转化研究。项目四：“改善患有良性乳腺疾病的女性的乳腺癌风险预测”解决了利用患者良性乳腺组织（BBD）中存在的特征更好地预测个体患者风险的高度重要的需求。该项目将使用大型马约BBD队列识别新的生物标志物并建立风险预测模型，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;。生物样本和病理学核心，以及核心C：生物统计学和患者登记核心。发展研究计划将继续确定和开发研究项目，这些项目最有希望推进到完整的SPORE项目，职业发展计划将继续确定和支持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。研究人员，核心设施和研究计划在SPORE都集成到MCCC，并共同将推进知识和研究结果转化为临床受益的妇女，或在风险，乳腺癌。

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.