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%的乳腺癌病例在50岁以后被诊断出来。 目前在美国，有超过380万乳腺癌幸存者，预计这一数字将 由于人口老龄化而急剧增加。化疗是一种非常有效的治疗乳腺癌的方法。 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 然而，乳腺癌最佳运动处方的证据表明， 幸存者有限。乳腺癌幸存者经常遭受长期的癌症治疗相关的副作用 (e.g.,身体功能障碍、严重疲劳、肌无力、周围神经病变和平衡障碍） 这可能与年龄相关的虚弱和流动性问题（50%的乳腺癌幸存者年龄较大）有关 60岁）。这些独特的挑战可能会限制锻炼的可行性，坚持性，进而影响疗效。高- 强度间歇训练（HIIT）作为一种时间效率高、潜在的上级训练方法，正引起越来越多的关注 有氧运动策略与中等强度持续训练（MICT）相比， 临床人群。我们最近调整HIIT和MICT的四肢非负重运动 (ANE)测力计，消除平衡问题，并分配工作之间的上部和下部 四肢，弥补虚弱和疲劳。我们的HIIT-ANE和MICT-ANE方案是新颖的， 为乳腺癌幸存者提供创新的运动干预。我们的中心假设是，HIIT-ANE将导致 与MICT-ANE相比，内皮和心脏功能的改善更大、更持久， 最近完成化疗的乳腺癌幸存者的常规护理（UC）。其目的是 应用程序是进行随机对照试验，以调查：1）短期和长期影响， HIIT-ANE、MICT-ANE和UC对内皮和心脏功能的影响;以及2）内皮和心脏功能的耐久性， HIIT-ANE与MICT-ANE的心脏效应。50岁及50岁以上妇女， 对于原发性、侵袭性、非转移性、I-III期乳腺癌， 随机分配至3组之一：HIIT-ANE、MICT-ANE或UC。运动训练将每周进行3天， 12个月的监督。主要关注的是通过血流评估的内皮和心脏功能- 介导的扩张和整体纵向应变。评估将在基线时进行， 12周的运动干预和12周的观察期后。为了获得机械的洞察力，我们将 研究循环血液生物标志物和内皮细胞中的关键生物标志物， 艺术血管内技术。这种探索性/发展性的R21将提供早期证据，说明我们的研究是否 有希望的HIIT-ANE在减轻乳腺癌后CVD风险方面比MICT-ANE和UC更有效 化疗我们的研究结果将为设计严格的全面临床试验奠定基础。