Mayo Clinic Breast Cancer SPORE

描述（由申请人提供）： 马约诊所乳腺癌SPORE由马约诊所癌症中心（MCCC）和马约基金会提交。该应用程序支持基础，临床和人口科学研究人员的多学科团队进行旨在减少乳腺癌负担和死亡率的转化研究。选择的转化研究项目代表了由SPORE研究人员进行的资助研究的延伸。SPORE的科学由四个转化研究项目组成。项目1“CHFR在乳腺癌肿瘤发生和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在控制有丝分裂进展中的分子作用，检查其对乳腺癌发展的贡献，并评估其作为紫杉醇治疗转移性乳腺癌女性的预测因素。项目2“BRCA2错义突变和乳腺癌”解决了哪些BRCA2错义突变易患癌症以及哪些是中性的这一至关重要的问题。这些研究涉及使用遗传和功能测定数据开发风险评估模型，并将直接转化为具有这些突变的患者。项目3“MUC 1糖肽疫苗策略在乳腺癌中的临床前和临床研究”旨在利用源自MUC 1序列的糖基化肽开发一种最佳的乳腺癌疫苗，该序列在超过90%的乳腺癌中过度表达和异常糖基化。项目4“芳香化酶抑制剂、乳腺密度和血浆类固醇激素”评价芳香化酶抑制剂（Al）治疗对女性乳腺摄影乳腺密度的影响，与Al和类固醇激素的血浆水平有关，并将研究细胞色素P450酶系统中单倍型单核苷酸多态性的药物遗传学关联。这些研究项目将由三个核心支持：核心1：孢子管理，核心2：生物标本和患者登记，核心3：生物统计。已经建立了一个发展研究计划，以开发有前途的研究举措和职业发展计划将用于促进乳腺癌转化研究中最有前途的初级教师研究人员的研究和职业生涯。研究人员，核心设施和发展研究计划在SPORE都集成到MCCC，并共同将推进知识和研究结果转化为临床乳腺癌妇女的利益。

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.