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All-Extremity Exercise as a Novel Strategy for Optimizing Cardiovascular Function during Chemotherapy for Breast Cancer

全肢运动作为乳腺癌化疗期间优化心血管功能的新策略

基本信息

批准号：
10418617
负责人：
Demetra Christou
金额：
$ 19.06万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-07 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10418617
关键词：
Acute Address Adherence Adverse effects Aerobic Exercise Age Air Air Movements Blood Vessels Body Composition Breast Cancer Patient Breast Cancer survivor Cardiomyopathies Cardiotoxicity Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Chemotherapy-Oncologic Procedure Clinical Data Development Disease Dose Echocardiography Elderly Endothelium Equilibrium Event Exercise Exposure to Fatigue Female Financial compensation Foundations Frequencies Functional disorder Heart Rate Heart failure Human Intervention Lead Left Ventricular Ejection Fraction Limb structure Lower Extremity Malignant Neoplasms Measures Mediating Monitor Muscle Weakness Nausea Non-Insulin-Dependent Diabetes Mellitus Nonmetastatic Patient Schedules Patients Personal Satisfaction Phase III Clinical Trials Population Postmenopause Quality of life Randomized Randomized Controlled Clinical Trials Randomized Controlled Trials Regimen Research Resolution Risk Risk Factors Safety Supervision Testing Toxic effect Ultrasonography United States Upper Extremity Walking Work age related brachial artery cardiorespiratory fitness cardiovascular disorder prevention cardiovascular disorder risk chemotherapeutic agent chemotherapy design endothelial dysfunction exercise adherence exercise intervention exercise prescription exercise training fall risk fitness heart function hormone receptor-positive improved innovation malignant breast neoplasm middle age mortality myocardial damage novel novel strategies older patient prevent psychosocial receptor recruit sedentary side effect treadmill treatment as usual

项目摘要

ABSTRACT Currently, there are 3.5 million breast cancer survivors in the United States and this number is expected to increase dramatically. Early stage breast cancer survivors are more likely to die of cardiovascular disease (CVD) than breast cancer. Exposure to chemotherapy may exacerbate existing CVD risk factors or may lead to acute and long-term cardiovascular toxicity. Studies on the cardiovascular impact of chemotherapy have typically focused on acute cardiotoxic effects. However, the vascular impact of chemotherapy, which may have longer term consequences, is not well characterized. Recently, there is increasing evidence that chemotherapy may cause endothelial dysfunction, a key early event in CVD development which leads to loss of atheroprotection and independently predicts CVD events and progression. Therefore, strategies to prevent CVD in breast cancer patients undergoing chemotherapy are clinically important. Aerobic exercise is considered safe during breast cancer chemotherapy and may be an effective strategy for guarding against cardiovascular toxicity but there are limited data in humans and no randomized controlled trials. Acute chemotherapy-induced side effects (e.g., fatigue, muscle weakness, balance problems, increased risk of falls) present unique challenges that may influence the feasibility and tolerability of exercise, and in turn its efficacy. We have recently developed an all- extremity non-weight-bearing exercise (ANE) intervention which is a promising novel and innovative exercise approach for breast cancer patients during chemotherapy and may be superior to other widely recommended forms of exercise. Our central hypothesis is that ANE will be feasible and will lead to greater cardiovascular protection during breast cancer chemotherapy and will be better tolerated than walking. The aims of this exploratory/developmental R21 application are to investigate in patients with primary non-metastatic breast cancer who are undergoing chemotherapy: 1) the effect of ANE, treadmill exercise (TE) and usual care (UC) on endothelial and cardiac function; and 2) the feasibility, tolerability and safety of ANE compared with TE. Breast cancer patients will be randomly assigned to receive 12 weeks of supervised ANE, TE or UC during chemotherapy. Exercise training will be supervised, and exercise prescription will be personalized to their initial fitness level and will gradually progress to 70% of peak heart rate, 50 min/session, 3 days/week. The primary focus will be on endothelial function assessed by brachial artery flow-mediated dilation via high-resolution ultrasonography and global longitudinal strain assessed by speckle tracking echocardiography. Cardiovascular assessments and other study measures will be completed before initiation of chemotherapy and after the intervention. Feasibility, tolerability, and safety will be monitored throughout the intervention. This exploratory/developmental R21 will provide early evidence on whether our promising ANE intervention is feasible, more effective in mitigating cardiovascular toxicity and better tolerated than TE during breast cancer chemotherapy. Our findings will lay the foundation for a Phase III clinical trial.

摘要目前，美国有350万乳腺癌幸存者，预计这一数字将急剧增加。早期乳腺癌幸存者更有可能死于心血管疾病（CVD）比乳腺癌更严重暴露于化疗可能会加剧现有的CVD风险因素或可能导致急性和长期心血管毒性。关于化疗对心血管影响的研究通常关注急性心脏毒性效应。然而，化疗对血管的影响，长期的后果，没有得到很好的表征。最近，越来越多的证据表明化疗可能导致内皮功能障碍，这是CVD发展的关键早期事件，导致动脉粥样硬化保护作用丧失并独立预测CVD事件和进展。因此，预防乳腺癌CVD的策略接受化疗的患者在临床上是重要的。有氧运动被认为是安全的，癌症化疗，可能是预防心血管毒性的有效策略，但人体数据有限，无随机对照试验。急性化疗引起的副作用（例如，疲劳、肌肉无力、平衡问题、增加的福尔斯风险）提出了独特的挑战，影响运动的可行性和耐受性，进而影响其功效。我们最近开发了一种- 肢体非负重运动（ANE）干预是一种很有前途的新型创新运动乳腺癌患者化疗期间的方法，并可能优于其他广泛推荐的上级锻炼的形式。我们的中心假设是ANE是可行的，并且会导致更大的心血管疾病。乳腺癌化疗期间的保护，将比步行更好地耐受。其目的是探索性/开发性R21应用旨在研究原发性非转移性乳腺癌患者正在接受化疗的癌症患者：1）ANE，跑步机运动（TE）和常规护理（UC）对内皮和心脏功能; 2）ANE与TE相比的可行性，耐受性和安全性。乳腺癌症患者将被随机分配接受12周的监督ANE，TE或UC，化疗运动训练将受到监督，运动处方将根据他们的初始健身水平，并将逐步进展到70%的峰值心率，50分钟/届，3天/周。主重点将是通过高分辨率肱动脉血流介导的舒张评估内皮功能超声检查和斑点追踪超声心动图评估的整体纵向应变。心血管评估和其他研究措施将在化疗开始前和化疗结束后完成。干预将在整个干预过程中监测可行性、耐受性和安全性。这探索性/发育性R21将提供早期证据，证明我们有希望的ANE干预是否是可行的，在减轻心血管毒性方面更有效，并且在乳腺癌期间比TE耐受性更好癌症化疗我们的发现将为III期临床试验奠定基础。