Phase II Trial of Aerobic Training in Metastatic Breast Cancer

描述(由申请人提供)：越来越多的人认识和接受乳腺癌诊断后锻炼的不可或缺的作用。这一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，而且观察数据表明，定期锻炼与乳腺癌确诊后女性癌症特异性和全因死亡率的大幅降低有关。在启动一项大规模随机对照试验研究运动对疾病结局的影响之前，首先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妇女中的安全性、可行性和潜在疗效。我们提出了一项随机的II期试验，以评估在HER-2阴性的转移性乳腺癌患者中，与单纯化疗(加注意对照)相比，在标准化疗方案中加入有氧训练的抗肿瘤活性和毒性。这笔赠款将有以下三个具体目标：(1)确定在接受转移性乳腺癌化疗的妇女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疗效(和变化)，以及(3)探索对乳腺癌进展和死亡的生物标记物(即炎症细胞因子和生长因子)的影响。这将是第一次调查这些问题的研究。 公共健康相关性：在诊断出早期乳腺癌(BC)后，人们越来越多地认识和接受锻炼的不可或缺的作用。尽管有这些积极的发现，但到目前为止还没有研究调查运动在被诊断为晚期(转移性)乳腺癌(MBC)的女性中的作用。早期BC的有力证据基础表明，运动可能是改善MBC功能能力和症状控制的适当支持性干预。然而，与早期研究相比，在MBC中进行的运动试验在疾病严重程度和临床预后、并存疾病的程度以及积极结合细胞毒性和支持性护理方案的先前和当前治疗方面构成了独特的挑战。因此，在启动一项明确的随机对照试验之前，首先要确定在这种环境下运动的可行性、安全性和初步效果。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的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.