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

增强对乳腺癌治疗期间心脏监测的危害和益处的了解

• 批准号: 10224673
• 负责人: Anthony Francis Yu
• 金额: $ 17.72万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224673
• 关键词: Address; Adherence; Adjuvant; Adult; Adverse effects; Anthracycline; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer therapy; Cancer Survivor; Cardiac; Cardiac Death; Cardiomyopathies; Cardiotoxicity; Cardiovascular system; Clinical; Clinical Investigator; Clinical Trials; Cost Savings; Detection; ERBB2 gene; Echocardiography; Enrollment; Ensure; Event; Foundations; Frequencies; Future; Goals; Guidelines; Health; Health Care Costs; Health Expenditures; Heart; Heart failure; Institution; Interruption; Intervention; Investigation; Knowledge; Lead; Left Ventricular Ejection Fraction; Life; Malignant Neoplasms; Mentors; Mentorship; Methods; Modeling; Monitor; Morbidity - disease rate; National Comprehensive Cancer Network; New York Heart Association Class III/IV; Newly Diagnosed; Observational Study; Oncology; Outcome; Paclitaxel; Participant; Patient-Focused Outcomes; Patients; Positive Test Result; Prevention strategy; Prospective Studies; Recommendation; Recording of previous events; Regimen; Reporting; Research; Research Design; Retrospective Studies; Retrospective cohort study; Risk; Safety; Savings; Scientist; Structure; Supervision; Testing; Training; Trastuzumab; Treatment-Related Cancer; United States Food and Drug Administration; Variant; Woman; Work; base; cancer therapy; cardiovascular risk factor; career; career development; chemotherapy; clinical practice; cost; economic impact; evidence base; evidence based guidelines; experience; health care service utilization; improved; malignant breast neoplasm; member; mortality; multidisciplinary; phase 2 study; primary outcome; prospective; response; safety and feasibility; skills; survivorship; treatment duration; trend

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.

项目概要/摘要 Yu 博士是纪念斯隆凯特琳 (MSK) 的成人心脏病专家，接受过超声心动图高级培训， 表现出对发展心脏肿瘤学临床研究人员职业生涯的坚定承诺。他的 长期目标是领导努力制定基于证据的预防、检测和预防策略 管理癌症治疗相关的心脏毒性，以减轻心血管竞争 癌症幸存者发病和死亡的原因。职业发展和培训计划概述 该应用程序经过量身定制，旨在为于博士提供必要的技能、结构化的指导和 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 作为临床科学家的独立性。多学科指导团队的成员由来自全国各地的 生存、心脏肿瘤学和健康结果领域公认的领导者致力于提供密切的服务 对于博士实现所有职业发展、培训和研究的监督和指导 本提案的目标。该提案科学方面的总体目标是更好地理解 曲妥珠单抗治疗期间与心脏监测相关的危害和益处。心脏毒性是好 公认的用于治疗 HER2 阳性乳腺癌的曲妥珠单抗疗法的不良反应。临床 曲妥珠单抗治疗期间心脏监测指南建议对左心室进行常规连续评估 心室射血分数（LVEF）。然而，有证据支持这一对所有人都适用的建议 曲妥珠单抗治疗的患者缺乏，特别是考虑到非蒽环类药物的使用呈增长趋势 基于曲妥珠单抗的治疗方案具有更安全的心脏毒性风险。虚假信息还存在潜在的危害—— 常规心脏监测期间检测到的阳性结果或临床上不显着的 LVEF 下降将 不必要地导致乳腺癌治疗和挽救生命的治疗中断或提前终止，并且 导致更糟糕的癌症结果。中心假设是，有限的心脏监测策略 心血管风险较低并接受非蒽环类曲妥珠单抗治疗方案的女性 将是安全且成本较低的。于博士将使用两种不同且互补的方法来解决这一中心假设 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 MSK 斯隆回顾性地研究了遵守心脏监测指南与 心脏毒性事件。在目标 2 中，承认回顾性研究设计的局限性，他将 前瞻性评估有限心脏监测策略对接受治疗的患者的安全性和可行性 基于非蒽环类曲妥珠单抗的治疗方案。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和有限的心脏监测策略相关。所获得的知识 心脏监测的危害和益处将为制定循证建议奠定基础 用于乳腺癌治疗期间的心脏监测。

项目成果

ARIC Welcomes Cancer Survivors Into Their Communities: Unraveling the Link Between Cancer and Cardiovascular Disease.

ARIC 欢迎癌症幸存者加入他们的社区：揭示癌症与心血管疾病之间的联系。

• DOI: 10.1016/j.jacc.2022.04.041
• 发表时间: 2022
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Yu,AnthonyF;Steingart,RichardM
• 通讯作者: Steingart,RichardM

Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation.

• DOI: 10.1016/j.echo.2017.08.017
• 发表时间: 2018-01
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Pun SC;Landau HJ;Riedel ER;Jordan J;Yu AF;Hassoun H;Chen CL;Steingart RM;Liu JE
• 通讯作者: Liu JE

Cardiac safety of non-anthracycline trastuzumab-based therapy for HER2-positive breast cancer.

基于非蒽环类曲妥珠单抗治疗 HER2 阳性乳腺癌的心脏安全性。

• DOI: 10.1007/s10549-017-4362-x
• 发表时间: 2017
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Yu,AnthonyF;Mukku,RoyB;Verma,Shivani;Liu,JenniferE;Oeffinger,KevinC;Steingart,RichardM;Hudis,CliffordA;Dang,ChauT
• 通讯作者: Dang,ChauT

Racial and Socioeconomic Disparities in Cardiotoxicity Among Women With HER2-Positive Breast Cancer.

• DOI: 10.1016/j.amjcard.2021.02.013
• 发表时间: 2021-05-15
• 期刊: The American journal of cardiology
• 作者: Al-Sadawi M;Hussain Y;Copeland-Halperin RS;Tobin JN;Moskowitz CS;Dang CT;Liu JE;Steingart RM;Johnson MN;Yu AF
• 通讯作者: Yu AF