Reducing Breast Cancer Recurrence with Weight Loss: A Vanguard Trial

描述(申请人提供)：乳腺癌的高发病率，加上更早的诊断和更有效的治疗，导致超过250万美国妇女现在是乳腺癌幸存者。过度肥胖是绝经前和绝经后乳腺癌患者确诊后的一个主要不良预后因素，在不同少数群体的女性中可能尤其相关。尽管有潜在的重要性，但从来没有临床试验来确定减肥和保持减肥是否可以降低复发风险。肥胖和缺乏运动与乳腺癌复发风险增加有关的机制尚不完全清楚，但包括更高的内源性雌激素和胰岛素，以及细胞因子和其他因素的变化。多达30%的乳腺癌幸存者经历了持续到治疗完成后的烦躁不安，可能具有临床意义。肥胖的乳腺癌幸存者的体重减轻和体力活动增加，可能会对心理社会问题和并存的医疗条件产生有利影响。我们建议对800名超重或肥胖(体重指数27和体重40公斤/平方米)的21岁及以上被诊断为IC、II或IIIA期乳腺癌的女性进行为期4年的试验。该项目的主要具体目标是：(1)在800名乳腺癌幸存者中进行一项以体重减轻为主要终点的为期4年的先锋随机对照试验，在随机后对所有受试者进行2年的跟踪调查。我们的主要假设是，在这一目标人群中，至少可以实现并保持7%的体重减轻。次要目标是：(2)使用REACH，Efficient/Efficient，Adept，Implementation，and Maintenance(RE-AIM)框架进行成本-效果分析，包括评估干预对医疗并存条件的影响；(3)评估干预对生活质量(QOL)的影响，特别是身体功能和疲劳；以及(4)前瞻性收集血液和DNA样本，以便能够分析潜在机制和不同亚组之间的差异反应。我们的研究策略加入了来自五个领先癌症中心的经验丰富的研究人员，他们是一个多学科团队，在饮食和运动干预、癌症生存、营养流行病学、乳腺肿瘤学试验和乳腺癌结果研究方面拥有出色的经验。减肥干预利用了基于认知行为的团体计划、电话咨询和基于家庭的支持，这些都是在项目调查人员之前进行的成功研究中开发和测试的。作为一项先锋试验，该项目将使用可在临床实践和社区项目中广泛采用的可访问策略来测试干预措施，并进行战略性设计，以导致对2500名受试者进行全面的癌症结果试验。如果我们期望发现的生活质量的改善能够在这项对800名幸存者的试验中得到证明，这一发现本身可能会改变临床实践的规范。如果最终的全面试验可以证明使用同样的干预措施可以降低复发风险，这项试验将启动为乳腺癌幸存者建立体重控制支持的努力，作为一种新的护理标准。

DESCRIPTION (provided by applicant): The high incidence of breast cancer coupled with earlier diagnosis and more effective therapies has resulted in over 2.5 million American women who are now breast cancer survivors. Excess adiposity is a major adverse prognostic factor post-diagnosis for women with both pre- and postmenopausal breast cancer and may be particularly relevant among women of various minority groups. Despite potential importance, there has never been a clinical trial to determine whether weight loss and maintenance of that loss reduces recurrence risk. Mechanisms that tie adiposity and physical inactivity to increased risk of breast cancer recurrence are not fully understood but include higher endogenous estrogens and insulin, and alterations in cytokines and other factors. Up to 30% of breast cancer survivors experience dysphoria that endures beyond completion of treatment and may be of clinical significance. Psychosocial problems and comorbid medical conditions are likely to be favorably affected by weight loss and increased physical activity in obese breast cancer survivors. We propose a 4-year trial of 800 overweight or obese (BMI >27 and <40 kg/m2) women aged 21 and older who have been diagnosed with stage IC, II, or IIIA breast cancer. The primary specific aim of the project is: (1) To conduct a 4-year vanguard randomized controlled trial with the primary endpoint of weight loss among 800 breast cancer survivors, following all subjects for 2 years after randomization. Our primary hypothesis is that weight loss of at least 7% can be achieved and maintained in this target population. Secondary aims are: (2) To use the Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to conduct a cost-effectiveness analysis that includes an assessment of the impact of the intervention on medical comorbid conditions; (3) To assess the impact of the intervention on quality of life (QOL), particularly physical functioning and fatigue; and (4) To prospectively collect blood and DNA samples to enable analysis of potential mechanisms and differential response across subgroups. Our research strategy joins experienced investigators from five of the leading cancer centers, a multi-disciplinary team with outstanding experience in diet and exercise interventions, cancer survivorship, nutritional epidemiology, breast oncology trials, and breast cancer outcomes research. The weight loss intervention utilizes a cognitive-behavioral group-based program, telephone counseling and home-based support, developed and tested in previous successful studies conducted by the project investigators. As a vanguard trial, this project will test an intervention using accessible strategies that can be adopted widely in clinical practice and community-based programs and is strategically designed to lead to a fully-powered trial of 2500 subjects for cancer outcomes. If the improvements in QOL that we expect to find can be demonstrated in this trial of 800 survivors, this finding could itself change the norms of clinical practice. If the eventual full trial can document lower recurrence risk with this same intervention, this trial initiates the effort to establish weight control support for breast cancer survivors as a new standard of care.