Mayo Clinic Breast Cancer SPORE

描述(由申请人提供)： 梅奥诊所乳腺癌孢子由梅奥诊所癌症中心(MCCC)和梅奥基金会提交。该应用程序支持一个由基础、临床和人口科学研究人员组成的多学科团队，以执行旨在减少乳腺癌负担和死亡率的转化性研究。选定的翻译研究项目代表了孢子调查人员正在进行的资助研究的延伸。孢子科学由四个翻译研究项目组成。项目1“CHFR在肿瘤发生和乳腺癌紫杉醇敏感性中的作用”研究了CHFR，一种参与新的有丝分裂检查点途径的多肽。该项目将阐明CHFR在控制有丝分裂进程中的分子作用，研究其在乳腺癌发生中的作用，并评估其作为紫杉醇治疗的转移性乳腺癌患者的预测因素。项目2“BRCA2错义突变与乳腺癌”解决了一个至关重要的问题，即哪些BRCA2错义突变易患癌症，哪些是中性的。这些研究涉及使用遗传和功能分析数据开发风险评估模型，并将直接翻译给具有这些突变的患者。项目3“乳腺癌MUC1糖肽疫苗策略的临床前和临床研究”旨在利用来自MUC1序列的糖基化多肽开发一种最佳的乳腺癌疫苗，MUC1序列在90%以上的乳腺癌中过度表达和异常糖基化。项目4“芳香酶抑制剂、乳房密度和血浆类固醇激素”评估了芳香酶抑制剂(Al)治疗对女性乳房X光检查的影响与Al和类固醇激素水平的关系，并将研究细胞色素P450酶系统中单倍型单核苷酸多态与药物遗传学的关系。这些研究项目将得到三个核心的支持：核心1：孢子管理；核心2：生物检疫和病人登记；核心3：生物统计。已经建立了一个发展研究计划来开发有前途的研究计划，职业发展计划将被用来促进乳腺癌翻译研究中最有前途的初级教研员的研究和职业生涯。孢子中的研究人员、核心设施和开发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，造福于乳腺癌妇女。

DESCRIPTION (provided by applicant): The Mayo Clinic Breast Cancer SPORE is being submitted by the Mayo Clinic Cancer Center (MCCC) and Mayo Foundation. This application supports a multidisciplinary team of basic, clinical and population science investigators to perform translational research directed at reducing the burden and mortality from breast cancer. The translational research projects chosen represent extensions of funded research being conducted by SPORE investigators. The science of the SPORE consists of four translational research projects. Project 1 "The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast Cancer" examines Chfr, a polypeptide involved in a novel mitotic checkpoint pathway. This project will elucidate the molecular role of Chfr in the control of mitotic progression, examine its contribution to development of breast cancer and evaluate it as a predictive factor in women with metastatic breast cancer treated with paclitaxel. Project 2 "BRCA2 Missense Mutations and Breast Cancer" addresses the critically important question of which BRCA2 missense mutations predispose to cancer and which are neutral. These studies involve development of risk assessment models using genetic and functional assay data and will be directly translatable to patients with these mutations. Project 3 "Preclinical and Clinical Studies of MUC1 Glycopeptide Vaccine Strategies in Breast Cancer" is directed at developing an optimal breast-cancer based vaccine utilizing glycosylated peptides derived from the MUC1 sequence, which is over expressed and aberrantly glycosylated in over 90% of breast cancers. Project 4 "Aromatase Inhibitors, Breast Density and Plasma Steroid Hormones" evaluates the impact of aromatase inhibitor (Al) therapy on mammographic breast density in women in relation to plasma levels of the Al and steroid hormones and will examine pharmacogenetic associations of haplotype single nucleotide polymorphisms in the cytochrome P450 enzyme system. These research projects will be supported by three cores: Core 1: SPORE Administration, Core 2: Biospecimens and Patient Registry, and Core 3: Biostatistics. A Developmental Research Program has been established to develop promising research initiatives and a Career Development Program will be used to promote the research and career of the most promising junior faculty investigators in breast cancer translational research. The investigators, core facilities, and the developmental 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 breast cancer.