A Randomized Trial to Minimize Non-Response to Aerobic Training in Operable Breast Cancer

项目总结 心血管疾病是早年晚期死亡(Death≥5年后死亡)的主要原因 乳腺癌(EBC)。有效的治疗策略，改善多个系统的功能是主要的 临床上需要减少EBC中的CVD。有氧运动疗法(AT)是一种多效性干预措施 改善心肺功能(CRF)的随机对照试验(RCT)是一种强大的、独立的预测因素 不列颠哥伦比亚省和其他恶性肿瘤的心血管疾病和全因死亡。然而，几乎所有肿瘤学的AT随机对照试验 报告总体队列的平均CRF变化；平均结果的显示掩盖了 回应。为了直接解决这一差距，我们的团队探索了最近完成的随机对照试验中的反应可变性 在174名EBC患者中(2.8岁。辅助治疗后)，他们被分配到150分钟/周：(1)线性AT (2)非线性AT(55%至100%CRF)；或(3)连续16周的伸展(注意力控制)。 尽管AT依从性很高，但我们发现：(1)CRF变化在-10%到+24%之间，(2)~60%是 根据CRF技术误差(TE；生物学的稳健衡量标准)被归类为CRF无应答者 可变性和测量误差)。这些发现表明AT遵循常规容量(~150 分钟/周)和/或长度(~16周)不足以改善相当大比例的EBC幸存者的CRF。 血管紧张素转换酶诱导的慢性肾衰的改善与心血管疾病风险的相应降低有关；因此，存在 迫切需要测试可优化CRF应答率的替代AT方法的有效性。初步 我们小组和其他人的研究结果表明，为了增加CRF，增加AT音量和/或 需要长度以允许多系统适应(即，跨心肺的所有组件- 血管-肌轴)。目前还没有RCT直接评估CRF的AT长度和容量 任何癌症人群的应答率。因此，本研究的目的是评估AT的效果 计划长度和数量对CRF应答率和EBC中其他相关结果的影响。目标1：比较 非线性AT程序长度和体积对CRF应答率的影响目标2：评估对 慢性肾功能衰竭的生理决定因素。目标3：确定患者报告的结果、可行性、 和安全。使用4臂随机对照试验设计，我们将随机分配152名(n=38)EBC幸存者如下 完成辅助治疗：手臂A：仅容量(每周300分钟，持续16周)，手臂B：仅长度(150 32周为分钟/周)、臂C：长度和体积(32周为300分钟/周)或臂D：对照组(150分钟/周 16周)。影响：这项研究的结果将确定最大化CRF应答的AT方案 Rate和其他临床相关的EBC终点。最终，这些发现将为以证据为基础的政策提供依据 指南和标准的临床护理。

PROJECT SUMMARY Cardiovascular disease (CVD) is the primary cause of late mortality (death ≥5 yrs from diagnosis) in early breast cancer (EBC). Effective treatment strategies that improve function across multiple systems are a major clinical need to reduce CVD in EBC. Aerobic exercise therapy (AT) is a pleiotropic intervention demonstrated in randomized controlled trials (RCTs) to improve cardiorespiratory fitness (CRF), a strong, independent predictor of CVD and all-cause mortality in BC and other malignancies. However, virtually all AT RCTs in oncology report the mean CRF change for the overall cohort; presentation of the mean result masks variability in responses. To directly address this gap, our group explored response variability in our recently completed RCT among 174 EBC patients (2.8 yrs. post-adjuvant therapy) who were allocated to 150 min/wk of: (1) linear AT (70% CRF); (2) nonlinear AT (55% to 100% CRF); or (3) stretching (attention control) for 16 consecutive wks. Despite high AT adherence, we found that: (1) CRF change ranged from -10% to +24%, and (2) ~60% were classified as CRF non-responders based on the CRF technical error (TE; a robust measure of biological variability and measurement error). These findings indicate that AT following the conventional volume (~150 min/wk) and / or length (~16 wks) is insufficient for improving CRF in a substantial proportion of EBC survivors. AT-induced improvement in CRF is associated with corresponding reductions in CVD risk; thus, there is a critical need to test the efficacy of alternative AT approaches that can optimize CRF response rate. Preliminary findings from our group, and others, indicate that in order to augment CRF, increased AT volume and / or length is required to allow for multisystem adaptation (i.e., across all components of the cardiopulmonary- vascular-muscular axis). There have been no RCTs directly assessing AT length and volume on CRF response rate in any cancer population. The objective of this study is therefore to evaluate the effects of AT program length and volume on CRF response rate and other pertinent outcomes in EBC. AIM 1: Compare the effects of nonlinear AT program length and volume on CRF response rates. AIM 2: Evaluate the effects on physiological determinants of CRF. AIM 3: Ascertain the difference in patient-reported outcomes, feasibility, and safety. Using a 4-arm RCT design, we will randomly allocate 152 (n=38/group) EBC survivors following completion of adjuvant therapy to: Arm A: volume only (300 min/wk for 16 weeks), Arm B: length only (150 min/wk for 32 weeks), Arm C: length and volume (300 min/wk for 32 weeks), or Arm D: control (150 min/wk for 16 weeks). IMPACT: Results from this investigation will identify the AT regimen that maximizes CRF response rate and other clinically relevant endpoints in EBC. Ultimately, these findings will inform policy, evidence-based guidelines, and standard clinical care.