Mayo Clinic Breast Cancer SPORE

梅奥诊所乳腺癌孢子的续期申请是在梅奥诊所癌症中心(MCCC)和梅奥基金会的全力支持下提交的，旨在继续旨在减少乳腺癌负担和死亡率的转化研究。孢子科学包括四个转译研究项目：项目1：“BRCA1和BRCA2乳腺癌易感基因中具有不确定意义的变种(VU)携带者的风险评估”将继续这项具有临床重要性和高度转译的研究，以解决许多女性在BRCA1/2检测和VUS结果出来后确定其个人乳腺癌风险的明显未得到满足的需求。项目2：《作为一种治疗乳腺癌的新激素疗法》是基于Mayo研究人员得出的临床前数据，表明Enoxifen具有比他莫昔芬更好的抗肿瘤活性。这些数据导致NCI开发临床级别的endoxifen，它将用于这个孢子项目的第一个人类阶段临床试验。项目3：“胰岛素样生长因子和胰岛素系统信号对激素抵抗乳腺癌的调节”集中于一种新的方法来处理激素治疗的抵抗，重点是胰岛素受体A异构体作为胰岛素生长因子通路信号的(共同)中介的作用。计划进行更多的临床前研究，完整的IGF和雌激素受体阻断将在II期临床试验中进行检查，该试验以密集获取生物样本(包括活检)而闻名，用于联合领导实验室的翻译研究。项目4：“改善患有良性乳腺疾病的妇女的乳腺癌风险预测”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的风险这一非常重要的需求。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，随后在孢子-孢子协作中进行验证。这些研究项目得到了三个高度互动的核心的支持：核心A：行政核心、核心B；生物医学和病理学核心，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最有希望进入全孢子项目的研究项目，职业发展计划将继续确定和支持乳腺癌转译研究中最有潜力成为未来孢子领导者的教职员工。孢子中的研究人员、核心设施和研究项目都被整合到MCCC中，共同促进知识进步并将研究结果转化为临床，造福于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.