High Intensity Interval Training: Optimizing Exercise Therapy to Mitigate Cardiovascular Disease Risk Following Breast Cancer Chemotherapy

高强度间歇训练：优化运动疗法以降低乳腺癌化疗后的心血管疾病风险

• 批准号: 10667675
• 负责人: Demetra Christou
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667675
• 关键词: Acceleration; Acute; Address; Adherence; Aerobic Exercise; Age; Age Years; Aging; Apoptosis; Attention; Biological Markers; Blood; Breast Cancer Risk Factor; Breast Cancer Treatment; Breast Cancer survivor; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Compensation; Coronary Arteriosclerosis; Data; Development; Diagnosis; Echocardiography; Elderly; Endothelial Cells; Endothelium; Equilibrium; Exercise; Exercise Therapy; Fatigue; Foundations; Functional disorder; Future; Harvest; Heart failure; Injury; Interval training; Intervention; Limb structure; Lower Extremity; Mediating; Muscle Weakness; Myocardial; Non-Insulin-Dependent Diabetes Mellitus; Nonmetastatic; Participant; Pathway interactions; Patients; Peripheral Nervous System Diseases; Pilot Projects; Population; Randomized; Randomized Controlled Clinical Trials; Randomized, Controlled Trials; Recommendation; Research; Resolution; Risk; Supervision; Techniques; Time; Toxic effect; Training; Treatment-Related Cancer; Ultrasonography; Upper Extremity; Woman; Work; age related; brachial artery; breast cancer diagnosis; cardiovascular disorder prevention; cardiovascular disorder risk; chemotherapy; design; effective therapy; equilibration disorder; evidence base; exercise intervention; exercise prescription; exercise regimen; exercise training; fall risk; frailty; heart function; human old age (65+); improved; innovation; insight; malignant breast neoplasm; minimally invasive; novel; premature; prevent; side effect; success; treatment as usual

PROJECT SUMMARY Aging is a major risk factor for breast cancer and 80% of breast cancer cases are diagnosed after age 50. Currently in the US, there are more than 3.8 million breast cancer survivors, and this number is expected to increase dramatically due to the aging of the population. Chemotherapy is a highly effective treatment for breast cancer but is associated with acute and long-term cardiovascular toxicity that may accelerate cardiovascular aging, thus setting the stage for premature development of cardiovascular disease (CVD). Aerobic exercise is recommended for CVD prevention, however, evidence on the optimal exercise prescription in breast cancer survivors is limited. Breast cancer survivors often suffer from long-lasting cancer therapy-related side effects (e.g., physical dysfunction, severe fatigue, muscle weakness, peripheral neuropathy, and balance impairments) that may be compounded by age-related frailty and mobility issues (50% of breast cancer survivors are older than age 60). These unique challenges may limit exercise feasibility, adherence, and in turn efficacy. High- intensity interval training (HIIT) is attracting increasing attention as a time-efficient and potentially superior aerobic exercise strategy for CVD prevention compared to moderate-intensity continuous training (MICT) in clinical populations. We have recently adapted HIIT and MICT on an all-extremity non-weight-bearing exercise (ANE) ergometer that eliminates balance concerns and distributes work between the upper and lower extremities, compensating for weakness and fatigue. Our HIIT-ANE and MICT-ANE regimens are novel and innovative exercise interventions for breast cancer survivors. Our central hypothesis is that HIIT-ANE will result in greater and more durable improvements in endothelial and cardiac function compared with MICT-ANE and usual care (UC) in breast cancer survivors who have recently completed chemotherapy. The aims of this application are to conduct a randomized controlled trial to investigate: 1) the short-term and prolonged effects of HIIT-ANE, MICT-ANE and UC on endothelial and cardiac function; and 2) the durability of the endothelial and cardiac effects of HIIT-ANE vs. MICT-ANE. Women, 50 years of age and older, who have completed chemotherapy within the past 6 months for primary, invasive, non-metastatic, stage I-III breast cancer will be randomized to 1 of 3 groups: HIIT-ANE, MICT-ANE or UC. Exercise training will be performed 3 days/week over 12 weeks under supervision. The primary focus will be on endothelial and cardiac function assessed by flow- mediated dilation and global longitudinal strain, respectively. Assessments will be performed at baseline, after the 12-week exercise intervention and after a 12-week observation period. To gain mechanistic insight, we will investigate circulating blood biomarkers and key biomarkers in endothelial cells harvested using a state-of-the- art endovascular technique. This exploratory/developmental R21 will provide early evidence on whether our promising HIIT-ANE is more effective in mitigating CVD risk than MICT-ANE and UC following breast cancer chemotherapy. Our findings will lay the foundation for designing a rigorous full-scale clinical trial.

项目摘要 衰老是乳腺癌的主要危险因素，80％的乳腺癌病例被诊断出50岁。 目前在美国，有超过380万乳腺癌幸存者，这一数字有望 由于人口的衰老而大大增加。化学疗法是对乳房的高效治疗 癌症，但与急性和长期心血管毒性有关，可能会加速心血管 衰老，从而为心血管疾病（CVD）的过早发展奠定了基础。有氧运动是 但是，建议用于预防CVD 幸存者是有限的。乳腺癌幸存者经常患有持久的癌症治疗相关副作用 （例如，身体功能障碍，严重疲劳，肌肉无力，周围神经病和平衡障碍） 与年龄相关的脆弱和流动性问题可能会使这种情况更加复杂（乳腺癌幸存者中有50％的人年龄较大 超过60岁）。这些独特的挑战可能会限制行使可行性，依从性和效力。高的- 强度间隔训练（HIIT）正在吸引越来越多的关注，作为时间效率且潜在的优越性 与中等强度连续训练（MICT）相比 临床人群。我们最近对HIIT和MICT进行了调整 （ANE）消除平衡问题并分配上层和下部之间的工作 四肢，补偿弱点和疲劳。我们的Hiit-ane和Mict-ane方案是新颖的， 乳腺癌幸存者的创新运动干预措施。我们的中心假设是Hiit-ane会导致 与Mict-ane和 最近完成化疗的乳腺癌幸存者的常规护理（UC）。这个目的 应用是进行随机对照试验进行调查：1） Hiit-ane，Mict-ane和UC在内皮和心脏功能上； 2）内皮和 HIIT-an-and vs. mict-ane的心脏影响。妇女，50岁及以上的妇女已经完成 在过去6个月内，用于原发性，侵入性，非转移性，I-III期乳腺癌的化学疗法将是 随机分为3组中的1个：Hiit-ane，mict-ane或UC。锻炼训练将每周3天进行 在监督下12周。主要重点将放在通过流量评估的内皮和心脏功能上 分别介导的扩张和全球纵向菌株。评估将在基线上进行 在12周的观察期间进行了为期12周的运动干预。为了获得机械洞察，我们将 研究使用最先进的内皮细胞中循环的血液标志物和关键生物标志物 艺术血管内技术。这种探索性/发展性R21将提供早期证据，证明我们的 有希望的Hiit-ane在减轻CVD风险方面比Mict-ane和UC更有效 化学疗法。我们的发现将为设计严格的全面临床试验奠定基础。