Randomized Trial of Optimal Type of Aerobic Training in Breast Cancer

描述(由申请人提供)：心肺功能(VO2峰值)是诊断乳腺癌(BC)后的一个极其重要的临床终点。VO2峰值是早期BC患者总体生活质量、疲劳感和其他患者报告的结果(PRO)的有力预测指标。此外，VO2峰值还与BC预后和心血管疾病的生物标志物密切相关。最后，VO2峰值和其他心肺健康指标是非癌症人群心血管和全因死亡率的可靠预测指标，而定期锻炼(VO2峰值的一个主要决定因素)与患上BC的女性相比，死亡风险降低50%。显然，最佳改善VO2峰值的干预措施对患有BC的妇女有相当大的临床益处。在患有早期BC的女性中，中等强度的有氧训练与VO2峰值的改善有统计学意义，但幅度不大。根据这一数据，美国癌症协会和医学研究所发布了指南，建议所有癌症患者每周锻炼5天，每次30分钟，强度适中。然而，到目前为止，还没有研究调查有氧训练的水平和形式，这种训练能在任何癌症人群中产生VO2峰值和其他终点的最佳改善。我们提出了一项前瞻性的三臂随机试验，以比较两种有氧训练干预相对于注意力控制组在完成初级癌症治疗的早期BC患者中的效果。这笔赠款将有以下主要和次要目标：主要目标：相对于注意力控制，比较高强度训练和中等强度训练对VO2峰值的影响。次要目的：(1)检测VO2峰对生理介质的影响；(2)比较VO2峰对PRO的影响；(3)比较VO2峰对BC复发和死亡的生物标志物(代谢稳态和全身炎症)的影响。这项研究将解决几个基本但目前尚未回答的问题，即运动训练在乳腺癌管理中的作用。从这项临床试验中获得的信息将在未来计划的研究中为设计提供依据，进一步调查运动训练在乳腺癌存活期中的作用。最后，这些机械性的发现将为如何改进运动训练干预以最大限度地改善VO2峰值和相关结果提供洞察力。

DESCRIPTION (provided by applicant): Cardiorespiratory fitness (VO2peak) is a clinical endpoint of immense importance following a diagnosis of breast cancer (BC). VO2peak is a strong predictor of overall quality of life, fatigue and other patient-reported outcomes (PROs) among women with early-stage BC. Furthermore, VO2peak is also strongly correlated with biomarkers of BC prognosis and cardiovascular disease. Finally, VO2peak and other measures of cardiorespiratory fitness are well-established predictors of cardiovascular and all-cause mortality in noncancer populations while regular exercise (a major determinant of VO2peak) is associated with a 50% reduction in the risk of mortality, relative to inactive women, following a BC diagnosis. Clearly, interventions that optimally improve VO2peak stand to have considerable clinical benefit for women with BC. Moderate-intensity aerobic training is associated with statistically significant but modest improvements in VO2peak among women with early BC. Based on this data, the American Cancer Society and Institute of Medicine issued guidelines recommending that all cancer patients should exercise e5 days/week for e30 minutes at a moderate intensity. However, no study to date has investigated the level and format of aerobic training that produces optimal improvements in VO2peak and other endpoints in any cancer population. We propose a prospective, three-arm, randomized trial to compare the effects of two aerobic training interventions relative to an attention-control group among early-stage BC patients who have completed primary cancer therapy. This grant will have the following primary and secondary aims: Primary aim: To compare the effect of high-intensity training to moderate-intensity training, relative to attention-control, on VO2peak. Secondary aims: (1) to examine the effects on physiological mediators of VO2peak, (2) To compare the effects on PROs, (3) to compare the effects on biomarkers of BC recurrence and mortality (i.e., metabolic homeostasis and systemic inflammation). This study will address several fundamental but, currently unanswered questions regarding the role of exercise training in the management of breast cancer. Information gained from this clinical trial will inform the design in future-planned studies further investigating the role of exercise training across the breast cancer survivorship continuum. Finally, the mechanistic findings will provide insight into how to refine exercise training interventions to maximize improvements in VO2peak and associated outcomes.