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: 8447994
• 负责人: CHERYL L ROCK
• 金额: $ 105.52万
• 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 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8447994
• 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）：乳腺癌的高发病率加上早期诊断和更有效的治疗，导致超过 250 万美国女性现在成为乳腺癌幸存者。过度肥胖是绝经前和绝经后乳腺癌女性诊断后的一个主要不良预后因素，并且在各个少数群体的女性中可能尤其相关。尽管具有潜在的重要性，但从未进行过临床试验来确定减肥和维持体重是否会降低复发风险。肥胖和缺乏运动与乳腺癌复发风险增加之间的联系机制尚不完全清楚，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烦躁不安，这种烦躁情绪在治疗结束后仍持续存在，并且可能具有临床意义。肥胖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合并症产生有利影响。我们建议对 800 名 21 岁及以上、被诊断患有 IC、II 或 IIIA 期乳腺癌的超重或肥胖（BMI > 27 且 < 40 kg/m2）女性进行一项为期 4 年的试验。该项目的主要具体目标是：(1) 开展一项为期 4 年的先锋随机对照试验，主要终点为 800 名乳腺癌幸存者的体重减轻，随机化后对所有受试者进行 2 年的跟踪。我们的主要假设是，该目标人群可以实现并维持至少 7% 的体重减轻。次要目标是： (2) 使用范围、功效/效果、采用、实施和维护 (RE-AIM) 框架进行成本效益分析，包括评估干预措施对医疗共存疾病的影响； (3) 评估干预措施对生活质量（QOL）的影响，特别是身体机能和疲劳； (4) 前瞻性地收集血液和 DNA 样本，以便分析亚组之间的潜在机制和差异反应。我们的研究策略由来自五个领先癌症中心的经验丰富的研究人员组成，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果研究方面拥有出色的经验。减肥干预措施采用了基于认知行为的团体计划、电话咨询和家庭支持，这些都是项目研究人员在之前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行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果试验。如果我们期望的生活质量改善能够在这项针对 800 名幸存者的试验中得到证实，那么这一发现本身就可能改变临床实践的规范。如果最终的全面试验可以证明通过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。

项目成果

Effect of weight loss on bone health in overweight/obese postmenopausal breast cancer survivors.

减肥对超重/肥胖绝经后乳腺癌幸存者骨骼健康的影响。

• DOI: 10.1007/s10549-015-3496-y
• 发表时间: 2015
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Toriola,AdetunjiT;Liu,Jingxia;Ganz,PatriciaA;Colditz,GrahamA;Yang,Lin;Izadi,Sonya;Naughton,MichaelJ;Schwartz,AnnaL;Wolin,KathleenY
• 通讯作者: Wolin,KathleenY

To Your Health: How Does the Latest Research on Alcohol and Breast Cancer Inform Clinical Practice?

• DOI: 10.1200/jco.2013.49.0466
• 发表时间: 2013-06-01
• 期刊: JOURNAL OF CLINICAL ONCOLOGY
• 影响因子: 45.3
• 作者: Demark-Wahnefried, Wendy;Goodwin, Pamela J.
• 通讯作者: Goodwin, Pamela J.