Phase II Trial of Aerobic Training in Metastatic Breast Cancer

描述（由申请人提供）：越来越多的人认识到和接受乳腺癌诊断后运动的整体作用。这种新出现的教条在很大程度上是基于随机试验的证据，这些证据表明，锻炼可以改善症状控制，同时观察数据表明，定期锻炼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。在开展一项调查运动对疾病预后影响的大规模随机对照试验之前，首先至关重要的是收集信息丰富的试点数据，以确定运动训练对接受化疗的转移性疾病女性的安全性、可行性和潜在疗效。我们提出了一项随机II期试验，以评估在标准化疗方案中增加有氧训练的抗肿瘤活性和毒性，相对于单独化疗（加注意力控制），在72名HER-2阴性转移性乳腺癌女性中。这项资助将有以下三个具体目的：(1)确定在转移性乳腺癌接受化疗的女性中进行监督有氧训练的可行性和安全性；(2)量化监督有氧训练对患者报告的结果和心肺功能变化的潜在功效（和变化）；(3)探索对乳腺癌进展和死亡率的生物标志物（即炎症细胞因子和生长因子）的影响。这将是第一个调查这些问题的研究。

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.