Enhancing Understanding of Harms and Benefits of Cardiac Monitoring During Breast Cancer Therapy

项目总结/摘要 博士Yu是Memorial Sloan Kettering（MSK）的成人心脏病专家，接受过超声心动图的高级培训， 已经证明了发展作为心脏肿瘤学临床研究者的职业生涯的坚定承诺。他 长期目标是领导制定循证战略，以预防、发现和 管理癌症治疗相关的心脏毒性，以减轻竞争性心血管 癌症幸存者发病率和死亡率的原因。职业发展和培训计划概述于 此应用程序已量身定制，为余博士提供必要的技能，结构化的指导， 研究经验，以满足他的长期研究和职业目标，并确保成功过渡到 作为临床科学家的独立性。多学科指导小组的成员， 在生存、心脏肿瘤和健康结果方面公认的领导者致力于提供密切的 监督和指导余博士在实现所有的职业发展，培训和研究 这一提案的目标。本提案科学方面的总体目标是更好地了解 曲妥珠单抗治疗期间与心脏监测相关的危害和益处。有毒物质是一种很好的 曲妥珠单抗治疗HER 2阳性乳腺癌的公认不良反应。临床 曲妥珠单抗治疗期间的心脏监测指南建议对左心室进行常规系列评估 心室射血分数（LVEF）。然而，支持这种一刀切的建议的证据 缺乏曲妥珠单抗治疗的患者，特别是考虑到非蒽环类药物的使用呈增长趋势， 基于曲妥珠单抗的方案具有更安全的心脏毒性风险特征。还有一个潜在的危害是虚假的- 常规心脏监测期间检测到的阳性结果或临床上不显著的LVEF下降将 不必要地导致治愈性和挽救生命的乳腺癌治疗中断或提前终止， 导致更糟糕的癌症结果。中心假设是， 接受非蒽环类曲妥珠单抗方案治疗的心血管风险低的女性 将是安全的，成本更低。余博士将使用两个不同的和互补的解决这个中心假设 接近。在目标1中，他将利用观察到的心脏监测频率的现有变化 在MSK回顾性研究心脏监测指南的依从性与 心脏毒性事件。在目标2中，认识到回顾性研究设计的局限性，他将 前瞻性评价有限心脏监测策略在接受以下治疗的患者中的安全性和可行性： 非蒽环类曲妥珠单抗为基础的方案。在目标3中，他将估计医疗保健利用率和成本 与基于指南的心脏监测策略相对于有限的心脏监测策略相关。从《圣经》中获得的知识 心脏监测的危害和益处将为制定基于证据的建议奠定基础 用于乳腺癌治疗期间的心脏监测。

PROJECT SUMMARY/ABSTRACT Dr. Yu, an adult cardiologist at Memorial Sloan Kettering (MSK) with advanced training in echocardiography, has demonstrated a strong commitment to developing a career as a clinical investigator in cardio-oncology. His long-term goal is to lead efforts to develop evidence-based strategies for the prevention, detection, and management of cancer therapy-associated cardiotoxicity in order to mitigate the competing cardiovascular causes of morbidity and mortality in cancer survivors. The career development and training plans outlined in this application have been tailored to provide Dr. Yu with the necessary skills, structured mentoring, and research experience to meet his long-term research and career goals and ensure a successful transition to independence as a clinician scientist. Members of a multidisciplinary mentorship team comprised of nationally recognized leaders in survivorship, cardio-oncology, and health outcomes are committed to providing close supervision and guidance to Dr. Yu in achieving all of the career development, training, and research objectives of this proposal. The overall objective of the scientific aspect of this proposal is to better understand the harms and benefits associated with cardiac monitoring during trastuzumab therapy. Cardiotoxicity is a well recognized adverse effect of trastuzumab therapy used to treat HER2-positive breast cancer. Clinical guidelines for cardiac monitoring during trastuzumab therapy recommend routine serial assessments of left ventricular ejection fraction (LVEF). However, evidence to support this one-size-fits-all recommendation for all patients treated with trastuzumab is lacking, particularly given the growing trend in the use of non-anthracycline trastuzumab-based regimens with safer cardiotoxicity risk profiles. There is also the potential harm that false- positive results or clinically insignificant LVEF declines detected during routine cardiac monitoring will unnecessarily lead to interruption or early termination of curative and life-saving breast cancer therapy and result in worse cancer outcomes. The central hypothesis is that a strategy of limited cardiac monitoring among women with a low cardiovascular risk profile and treated with a non-anthracycline trastuzumab-based regimen will be safe and less costly. Dr. Yu will address this central hypothesis using two distinct and complementary approaches. In Aim 1, he will capitalize on existing variations in the frequency of cardiac monitoring observed at MSK to retrospectively examine the association between adherence to cardiac monitoring guidelines and cardiotoxicity events. In Aim 2, acknowledging the limitations of a retrospective study design, he will prospectively evaluate the safety and feasibility of a limited cardiac monitoring strategy in patients treated with a non-anthracycline trastuzumab-based regimen. In Aim 3, he will estimate the healthcare utilization and costs associated with guideline-based versus limited cardiac monitoring strategies. The knowledge gained on the harms and benefits of cardiac monitoring will lay the groundwork to develop evidence-based recommendations for cardiac monitoring during breast cancer therapy.