Reducing Breast Cancer Recurrence with Weight Loss: A Vanguard Trial

通过减肥减少乳腺癌复发：先锋试验

• 批准号: 8239925
• 负责人: CHERYL L ROCK
• 金额: $ 122.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239925
• 关键词: 21 year old; Adopted; Adoption; Affect; Aftercare; American; Behavioral; Binding Proteins; Biochemical; Biological; Blood; Body Weight decreased; Body mass index; Breast; Breast Cancer Cell; Breast Cancer Treatment; Cancer Center; Cancer Survivor; Cancer Survivorship; Cardiac; Cardiology; Cardiovascular Diseases; Clinical Management; Clinical Trials; Cognitive; Communities; Comorbidity; Cost Effectiveness Analysis; Counseling; Coupled; DNA; Diabetes Mellitus; Diagnosis; Disease-Free Survival; Early Diagnosis; Economics; Effectiveness; Energy Intake; Energy Metabolism; Estrogens; Fatigue; Funding; Future; General Population; Genetic; Gonadal Steroid Hormones; Growth; Growth Factor; Health Services; Home environment; Hormones; Hyperinsulinism; Hypertension; Incidence; Insulin; Intervention; Intervention Trial; Lead; Link; Maintenance; Malignant Neoplasms; Medical; Minority Groups; Myocardial Infarction; Obesity; Observational Study; Outcome; Outcomes Research; Overweight; Patients; Physical Function; Physical activity; Postmenopause; Premenopause; Process; Prognostic Factor; Provider; Quality of life; Randomized; Randomized Controlled Trials; Recurrence; Rehabilitation therapy; Relative (related person); Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Sampling; Staging; Subgroup; Survivors; Symptoms; Target Populations; Telephone; Testing; Time; Weight; Weight Gain; Weight maintenance regimen; Woman; base; breast cancer diagnosis; cancer recurrence; cancer therapy; clinical care; clinical practice; clinically significant; cost; cost effectiveness; cytokine; design; diet and exercise; dysphoria; effective therapy; energy balance; experience; improved; intervention effect; malignant breast neoplasm; mortality; nutritional epidemiology; oncology; programs; psychosocial; response; standard of care; weight loss intervention; weight maintenance

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.

描述（由申请人提供）：乳腺癌的高发病率以及较早的诊断和更有效的疗法导致了超过250万现在乳腺癌幸存者的美国妇女。过量肥胖是对绝经前和绝经后乳腺癌的女性诊断后诊断后的主要不良预后因素，并且在各个少数群体的妇女中可能尤其重要。尽管潜在的重要性，但从未进行过临床试验来确定减肥和维持这种损失是否会降低复发风险。将肥胖和身体不活跃的机制与增加的乳腺癌复发风险相关的机制尚不完全了解，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。多达30％的乳腺癌幸存者经历了吞咽困难，无法完成治疗的完成，并且可能具有临床意义。心理问题和合并症可能会受到体重减轻和肥胖乳腺癌幸存者体育锻炼增加的影响。我们提出了为期4年的21岁及以上妇女的超重或肥胖（BMI> 27和<40 kg/m2）的4年试验，她们被诊断为IC，II或IIIA乳腺癌。该项目的主要特定目的是：（1）进行4年的先锋随机对照试验，并在所有受试者随机两年后两年后，在800个乳腺癌幸存者中重量减轻的主要终点。我们的主要假设是，在该目标人群中可以实现和维持至少7％的体重。次要目的是：（2）使用覆盖范围，功效/有效性，采用，实施和维护（RE-AIM）框架进行成本效益分析，其中包括评估干预对医疗合并条件的影响； （3）评估干预对生活质量（QOL）的影响，尤其是身体功能和疲劳； （4）前瞻性收集血液和DNA样品，以分析潜在的机制和亚组之间的差异反应。我们的研究策略与来自五个领先的癌症中心的经验丰富的研究人员，这是一个多学科团队，在饮食和运动干预措施，癌症生存，营养流行病学，乳房肿瘤学试验和乳腺癌结果研究方面具有出色的经验。减肥干预措施利用了基于认知行为的群体计划，电话咨询和基于家庭的支持，并在项目调查人员进行的先前成功研究中进行了测试。作为Vanguard试验，该项目将使用可访问的策略测试一项干预措施，该策略可以在临床实践和基于社区的计划中广泛采用，并以战略性旨在导致对2500名癌症结果的2500名受试者进行全力驱动的试验。如果我们期望找到的QoL的改进可以在800名幸存者的试验中证明，那么这一发现本身可以改变临床实践的规范。如果最终的全面试验可以通过相同的干预措施记录较低的复发风险，则该试验将努力为乳腺癌幸存者建立体重控制支持作为新的护理标准。