Evaluation of Barriers to Completion of Breast Cancer Treatment at a Tertiary Teaching and Referral Center in Kenya

项目摘要/摘要：总体 这是范德比尔特-英格拉姆癌症中心(VICC)孢子在乳腺的第三次竞争性更新申请 癌症。利用非常活跃和强大的多学科乳腺癌VICC的成熟框架 在孢子机制的有力支持下，我们在目前的 项目期。我们非常成功的发展研究项目(DRP)和职业提升 项目(CEP)继续在转化型乳腺癌研究中催化新的想法和新的研究人员， 包括这一持续更新中的两个项目。我们正准备完成拟议的工作，并 在未来几年将更加高效，这要归功于特殊的多学科计划和 与其他乳腺癌项目和孢子以及国家和 国际合作。我们的总体目标保持不变：开展协作性、多学科和 基于机制的翻译研究将对患有或 有患乳腺癌的风险。经过重大规划和内部和外部顾问委员会的评估，我们 提出四个双向翻译项目，解决基础、翻译和临床研究问题 项目1和2是延续项目，项目3和4是新项目 在本供资周期内由两个CEP奖项演变而来的项目：项目1--机制 ER阳性乳腺癌患者对内分泌治疗的抵抗；项目2-改善TNBC预后的策略 患者整合特定亚型基因组和基于免疫的发现；项目3-靶向DNA 乳腺癌的损伤反应；项目4-靶向抗原呈递以改进免疫治疗 乳腺癌的反应。该应用程序还包括DRP和CEP，以及四个高度集成的共享 核心资源：管理和参与、生物统计学和生物信息学、病理学和组织学 信息学和免疫表型。这些核心带来了创新技术和资源，包括额外的 具有项目特定专业知识的人员提供给整个VICC乳房孢子计划，并且不要重复 VICC或范德比尔特大学医学中心(VUMC)提供的现有共享资源。重点放在 人类终点，六项介入治疗临床试验与高度翻译的项目相关 在这项提案中，所有这些都是基于世界级基础和临床研究人员之间的广泛合作。我们 已经牢固地建立了一支真正的多学科团队，成功地实施了创新的临床试验来测试 来自体外和患者研究的假设，并将继续产生富有成效的翻译 与其他乳腺癌项目和孢子以及国家和国际组织合作。

PROJECT SUMMARY/ABSTRACT: OVERALL This is the third competing renewal application of the Vanderbilt-Ingram Cancer Center (VICC) SPORE in Breast Cancer. Using the well-established framework of a very active and strong multidisciplinary VICC Breast Cancer Program that is robustly supported by the SPORE mechanism, we have made significant progress in our current project period. Our highly successful Developmental Research Projects (DRP) and Career Enhancement Programs (CEP) continue to catalyze new ideas and new investigators in translational breast cancer research, including two projects in this continuing renewal. We are uniquely poised to complete the proposed work and to be even more productive in the years to come, thanks to an exceptional multidisciplinary program and established productive collaborations with other Breast Cancer Programs and SPOREs, as well as national and international collaborations. Our overall goal remains the same: To conduct collaborative, multidisciplinary and mechanism-based translational research that will have the highest possible impact for women and men with or at risk for breast cancer. After significant planning and internal and external advisory board evaluation, we propose four bi-directional translational projects addressing basic, translational and clinical research questions of importance in human breast cancer; Projects 1 and 2 are continuation projects, Projects 3 and 4 are new projects that have evolved from two CEP awards in the current funding cycle: Project 1 - Mechanisms of Resistance to Endocrine Therapy in ER+ Breast Cancer; Project 2 - Strategies to Improve Outcomes for TNBC Patients Integrating Subtype-specific Genomic and Immune-based Discoveries; Project 3 - Targeting the DNA Damage Response in Breast Cancer; Project 4 - Targeting Antigen Presentation to Improve Immunotherapy Responses in Breast Cancer. The application also includes DRP and CEP, and four highly integrated shared core resources: Administration and Engagement, Biostatistics and Bioinformatics, Pathology and Tissue Informatics, and Immunophenotyping. The cores bring innovative technology and resources, including additional personnel with project-specific expertise, to the overall VICC Breast SPORE Program and do not duplicate pre- existing shared resources available at VICC or Vanderbilt University Medical Center (VUMC). With a focus on human endpoints, six interventional therapeutic clinical trials are associated with the highly translational projects in this proposal, all based on extensive collaboration between world-class basic and clinical investigators. We have firmly established a true multidisciplinary team that successfully implements innovative clinical trials to test hypotheses that result from in vitro and patient studies, and that will continue to have productive translational collaborations with other Breast Cancer Programs and SPOREs as well as national and international groups.