Phase II Trial of Aerobic Training in Metastatic Breast Cancer

描述（由申请人提供）：在乳腺癌诊断后，越来越多的人认识到和接受运动的不可或缺的作用。这种新出现的教条在很大程度上是基于随机试验的证据，表明运动可以改善症状控制，以及观察数据表明，定期运动与乳腺癌诊断后女性癌症特异性和全因死亡率的大幅降低有关。在启动一项大规模RCT调查运动对疾病结局的影响之前，首先至关重要的是收集信息丰富的试点数据，以确定运动训练在接受化疗的转移性疾病女性中的安全性、可行性和潜在疗效。我们提出了一项随机II期试验，以评估在72名HER-2阴性转移性乳腺癌妇女中，在标准化疗方案中加入有氧训练相对于单独化疗（加注意力控制）的抗肿瘤活性和毒性。这笔赠款将有以下三个具体目标：（1）确定接受转移性乳腺癌化疗的妇女进行监督有氧训练的可行性和安全性，（2）量化潜在疗效（和变化）监督有氧训练对患者报告的结果和心肺功能的变化，和（3）探索对乳腺癌进展和死亡率的生物标志物的影响（即，炎性细胞因子和生长因子）。这将是第一次研究这些问题。 公共卫生相关性：越来越多的人认识到和接受运动在早期乳腺癌（BC）诊断后的不可或缺的作用。尽管有这些积极的发现，但迄今为止还没有研究调查运动在诊断为晚期（转移性）乳腺癌（MBC）的女性中的作用。早期BC的强有力证据基础表明，运动可能是一种适当的支持性干预措施，以改善MBC的功能能力和症状控制。然而，相对于早期环境中的研究，MBC中的运动试验在疾病严重程度和临床预后、共病程度以及既往和当前积极的细胞毒性和支持性治疗方案联合治疗方面提出了独特的挑战。因此，在开展一项确定性随机对照试验之前，首先确定在这种情况下运动的可行性、安全性和初步疗效至关重要。为了解决这个问题，我们建议在72名接受MBC化疗的女性中进行一项随机II期试验。

DESCRIPTION (provided by applicant): There is growing recognition and acceptance of the integral role of exercise following a breast cancer diagnosis. This emerging dogma is based, in large part, on evidence from randomized trials indicating that exercise improves symptom control as well as observational data suggesting that regular exercise is associated with substantial reductions in cancer-specific and all-cause mortality in women following a breast cancer diagnosis. Prior to launching a large-scale RCT investigating the effects of exercise on disease outcome, it is first of crucial importance to gather informative pilot data to establish the safety and feasibility and potential efficacy of exercise training in women with metastatic disease undergoing chemotherapy. We propose a randomized phase II trial to assess the antitumor activity and toxicity of the addition of aerobic training to standard chemotherapeutic regimens relative to chemotherapy alone (plus attention-control) among 72 women with HER-2 negative metastatic breast cancer. This grant will have the following three specific aims: (1) to determine the feasibility and safety of supervised aerobic training among women undergoing chemotherapy for metastatic breast cancer, (2) to quantify the potential efficacy (and variation) of supervised aerobic training on changes in patient-reported outcomes and cardiopulmonary function, and (3) to explore the effects on biomarkers of breast cancer progression and mortality (i.e., inflammatory cytokines and growth factors). This will be the first study to investigate these questions. PUBLIC HEALT RELEVANCE: There is growing recognition and acceptance of the integral role of exercise following a diagnosis of early-stage breast cancer (BC). Despite these positive findings, no study to date has investigated the role of exercise among women diagnosed with advanced (metastatic) breast cancer (MBC). The strong evidence base in early-stage BC suggests that exercise may be an appropriate supportive intervention to improve functional capacity and symptom control in MBC. However, relative to studies in the early-stage setting, exercise trials in MBC pose a unique challenge with respect to disease severity and clinical prognosis, extent of comorbid disease, and prior and current treatment with aggressive combination cytotoxic and supportive care regimens. Thus, prior to launching a definitive RCT, it is first of critical importance to determine the feasibility, safety, and initial efficacy of exercise in this setting. To address this question, we propose a randomized phase II trial among 72 women undergoing chemotherapy for MBC.