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已经导致超过250万美国妇女成为乳腺癌幸存者。过度肥胖是绝经前和绝经后乳腺癌妇女诊断后的主要不良预后因素，可能与各种少数民族妇女特别相关。尽管有潜在的重要性，但从来没有临床试验来确定减肥和维持体重是否能降低复发风险。将肥胖和缺乏运动与乳腺癌复发风险增加联系起来的机制尚不完全清楚，但包括较高的内源性雌激素和胰岛素，以及细胞因子和其他因素的改变。高达30%的乳腺癌幸存者会经历焦虑症，这种焦虑症在治疗结束后仍然存在，可能具有临床意义。减肥和增加体育活动可能对肥胖乳腺癌幸存者的心理社会问题和合并症有积极影响。我们建议进行一项为期4年的试验，纳入800名年龄在21岁及以上、被诊断为IC期、II期或IIIA期乳腺癌的超重或肥胖（BMI为bbb27和<40 kg/m2）女性。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，功效/有效性，采用，实施和维护（RE-AIM）框架进行成本效益分析，包括评估干预对医疗合并症的影响；(3)评估干预对生活质量（QOL）的影响，特别是对身体功能和疲劳的影响；(4)前瞻性地收集血液和DNA样本，以分析潜在的机制和亚群之间的差异反应。我们的研究策略联合了来自五个领先癌症中心的经验丰富的研究人员，这是一个在饮食和运动干预、癌症生存、营养流行病学、乳腺癌肿瘤试验和乳腺癌结局研究方面具有杰出经验的多学科团队。减肥干预利用了认知行为小组为基础的项目、电话咨询和家庭支持，这些都是由项目调查员在之前的成功研究中开发和测试过的。作为一项先锋试验，该项目将使用可广泛应用于临床实践和社区项目的可访问策略来测试一种干预措施，并在战略上设计为2500名受试者的癌症结果进行全面试验。如果我们期望发现的生活质量的改善可以在800名幸存者的试验中得到证明，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能够证明同样的干预措施可以降低复发风险，那么该试验将开始努力为乳腺癌幸存者建立体重控制支持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.