Reducing Breast Cancer Recurrence with Weight Loss: A Vanguard Trial

描述（由申请人提供）：乳腺癌的高发病率加上早期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妇女诊断后的一个主要不良预后因素，在各种少数群体的妇女中可能特别相关。尽管潜在的重要性，从来没有一个临床试验，以确定是否减肥和维持这种损失减少复发的风险。肥胖和缺乏体力活动与乳腺癌复发风险增加相关的机制尚未完全了解，但包括内源性雌激素和胰岛素水平较高，以及细胞因子和其他因素的改变。高达30%的乳腺癌幸存者经历了超过治疗完成的烦躁不安，可能具有临床意义。肥胖乳腺癌幸存者的心理社会问题和共病医疗条件可能会受到减肥和增加体力活动的有利影响。我们计划对800名21岁及以上的超重或肥胖（BMI >27且<40 kg/m2）女性进行一项为期4年的试验，这些女性被诊断为IC、II或IIIA期乳腺癌。该项目的主要具体目的是：（1）在800名乳腺癌幸存者中进行一项为期4年的先锋随机对照试验，主要终点为体重减轻，随机化后随访所有受试者2年。我们的主要假设是，在该目标人群中可以实现并维持至少7%的体重减轻。次要目标是：（2）使用RE-AIM框架进行成本效益分析，包括评估干预措施对医疗共病的影响;（3）评估干预措施对生活质量的影响，特别是身体功能和疲劳;和（4）前瞻性采集血液和DNA样本，以便分析潜在机制和亚组间的差异反应。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，这是一个多学科团队，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局研究方面具有出色的经验。减肥干预利用认知行为小组为基础的程序，电话咨询和家庭为基础的支持，开发和测试在以前的成功研究进行的项目调查。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获得策略来测试干预措施，并在战略上设计为对2500名受试者进行全面的癌症结局试验。如果我们期望发现的生活质量改善可以在800名幸存者的试验中得到证实，这一发现本身就可以改变临床实践的规范。如果最终的完整试验可以证明使用相同的干预措施可以降低复发风险，则该试验将启动为乳腺癌幸存者建立体重控制支持作为新的护理标准的努力。

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.