Effects of Exercise on Changes in Cardiovascular Biomarkers in Patients with Breast Cancer During Anthracycline-based Chemotherapy

运动对蒽环类化疗期间乳腺癌患者心血管生物标志物变化的影响

• 批准号: 10579380
• 负责人: Anthony Francis Yu
• 金额: $ 8.85万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10579380
• 关键词: Acute; Address; Adjuvant; Adjuvant Chemotherapy; Adverse effects; Aerobic Exercise; Age; Anthracycline; Attenuated; Biological Markers; Biological Specimen Banks; Blood specimen; Brain natriuretic peptide; Breast Cancer Treatment; Breast Cancer therapy; CXCL10 gene; Cancer Control; Cancer Etiology; Cardiac; Cardiac Myocytes; Cardiopulmonary; Cardiotoxicity; Cardiovascular system; Characteristics; Clinical; Cyclic GMP; Data; Development; Dose; Early Diagnosis; Educational Intervention; Epidermal Growth Factor Receptor; Exercise; Future; Guidelines; Heart Injuries; Human; Hypertension; Impairment; Inflammation; Inflammatory; Infrastructure; Injury; Interleukin-6; Intervention Trial; Knowledge; Lung; Malignant Neoplasms; Measures; Myocardial; Myocardial dysfunction; Myocarditis; N-terminal; Natriuretic Peptides; Neoadjuvant Therapy; Oncology; Outcome; Pathway interactions; Patients; Physical activity; Physiological; Physiological Adaptation; Play; Publishing; Radiation therapy; Randomized; Randomized, Controlled Trials; Recommendation; Risk; Risk Factors; Role; Sampling; Skeletal Muscle; Stimulator of Interferon Genes; Stress; Toxic effect; Treatment Protocols; Troponin; Troponin I; Woman; biomarker performance; cancer survival; cancer therapy; cardioprotection; cardiorespiratory fitness; cardiovascular effects; cardiovascular injury; cell free DNA; chemotherapy; cytotoxic; deconditioning; design; exercise training; health related quality of life; improved; insight; malignant breast neoplasm; mortality; multimodality; myocardial injury; open label; patient subsets; prevent; risk prediction; sarcopenia; targeted agent; targeted treatment

PROJECT SUMMARY Anthracyclines and human epidermal growth factor receptor 2 (HER2)-targeted agents have improved overall breast cancer control and survival; however, the benefits of these cancer therapies are offset by cardiovascular (CV) toxicity that can occur acutely during therapy or years after completion. Our group has shown that chemotherapy for primary breast cancer causes both direct injury to the cardiac-lung-skeletal muscle axis (e.g. cytotoxic/targeted/radiation therapy-associated injury) and secondary adverse effects (e.g. deconditioning, sarcopenia) which lead to significant declines in cardiorespiratory fitness (CRF), an integrative measure of global cardiopulmonary function. We recently completed the Optimal Timing Trial, a randomized, open-label trial evaluating the tolerability and effects of three different AT sequencing strategies versus physical activity (PA) advice control on CRF in 158 women with early stage (I–III) breast cancer undergoing primary adjuvant or neoadjuvant chemotherapy (NCI R01CA164751, NCT01943695). The results demonstrated that AT during and after chemotherapy was safe and attenuated CRF decline compared to PA advice. However, a fundamental question related to AT is whether it is an effective strategy to mitigate the direct cardiac injury from anthracyclines and HER2-targeted therapy. To address this knowledge gap, we propose an ancillary biomarker study to the Optimal Timing Trial and will include CV biomarkers that are used for early detection of subclinical cardiotoxicity during cancer treatment and predictive of subsequent cardiac dysfunction. The overall objective of the proposed study is to determine the effects of AT during cardiotoxic breast cancer treatment on correlative measures of CV injury, stress, and inflammation. We will study a subset of 69 patients treated with anthracycline chemotherapy (with or without HER2-targeted therapy) who had blood samples collected pre- and post-chemotherapy (n = 138 total samples). The aims of our study are to: (1) determine the effect of AT on changes in CV biomarkers of myocardial injury (high-sensitivity troponin-I, cardiac cell-free DNA), stress (N- terminal pro B-type natriuretic peptide), and inflammation (CXCL10, IL-6); and (2) explore factors that modify the effect of AT on changes in CV biomarkers. The results of the study will provide insights on the impact of AT to prevent adverse CV effects of breast cancer therapy, improve understanding of the underlying mechanisms of AT-induced physiologic adaptation, and inform the design of future studies to mitigate the CV toxicity of cancer treatment.

项目摘要 蒽环类药物和人类表皮生长因子受体2（HER2）靶向剂的总体改善 乳腺癌控制和生存；但是，这些癌症疗法的好处被心血管所抵消 （CV）在治疗期间或完成后几年中可能急性发生的毒性。我们的小组表明 原发性乳腺癌的化学疗法既导致心脏肺肌肉肌轴直接损伤（例如 细胞毒性/靶向/放射治疗相关的损伤）和次要不良反应（例如，调节性， 肌肉减少症）导致心肺健康（CRF）显着下降，这是对 全局心肺功能。我们最近完成了最佳计时试验，这是一个随机，开放标签 在测序策略与体育锻炼中三个不同的耐受性和影响的试验 （PA）对CRF的建议控制158名早期（I – III）乳腺癌的咨询控制，接受初级调整或 新辅助化疗（NCI R01CA164751，NCT01943695）。结果表明在和 与PA建议相比，化学疗法是安全的，CRF的下降减弱。但是，这是一个基本 与AT相关的问题是，这是否是减轻直接心脏损伤的有效策略 蒽环类药物和靶向HER2靶向疗法。为了解决这个知识差距，我们提出了辅助生物标志物 研究最佳计时试验，并将包括用于早期检测的CV生物标志物 癌症治疗期间的心脏毒性并预测随后的心脏功能障碍。总体目标 拟议的研究是确定心脏毒性乳腺癌治疗中AT的影响 简历损伤，压力和炎症的相关度量。我们将研究69例接受治疗的患者的子集 蒽环类化学疗法（有或不接受Her2靶向疗法），他们的血液样本收集了 和化学后（n = 138个样本）。我们研究的目的是：（1）确定AT的影响 心肌损伤的CV生物标志物的变化（高敏感性肌钙蛋白I，无心脏细胞DNA），应激（N-） 末端pro b型纳地尿肽）和注射（CXCL10，IL-6）; （2）探索修改的因素 AT对CV生物标志物变化的影响。该研究的结果将为AT的影响提供见解 为了防止乳腺癌治疗的不良简历影响，请改善对基本机制的理解 诱导的生理适应，并告知未来研究的设计，以减轻CV的毒性 癌症治疗。