RCT of exercise on aromatase inhibitor side effects in breast cancer survivors

运动对乳腺癌幸存者芳香酶抑制剂副作用的随机对照试验

• 批准号: 7728942
• 负责人: Melinda L Irwin
• 金额: $ 68.92万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-06 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7728942
• 关键词: Address; Adjuvant; Adjuvant Study; Adjuvant Therapy; Adverse effects; Aerobic Exercise; American Society of Clinical Oncology; Anxiety; Aromatase Inhibitors; Arthralgia; Attention; Attenuated; Body Weight; Body Weight decreased; Bone Density; C-reactive protein; Cancer Patient; Cancer Survivor; Cancer Survivorship; Clinic Visits; Consensus; Control Groups; Coping Skills; Data; Degenerative polyarthritis; Diagnosis; Endocrine; Ensure; Estrogens; Exercise; Fatty acid glycerol esters; Fibromyalgia; Fracture; Health; Health education; Home environment; Hormone Receptor; Interleukin-6; Intervention; Mails; Maintenance; Mass in breast; Mediating; Mediator of activation protein; Methods; Mission; Muscle; Outcome Study; Pain; Pharmaceutical Preparations; Postmenopause; Progesterone Receptors; Quality of life; Randomized; Randomized Controlled Clinical Trials; Research; Rheumatoid Arthritis; Risk; Safety; Self Efficacy; Severities; Staging; Survivors; Tamoxifen; Toxic effect; Training Programs; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Walking; Woman; base; bisphosphonate; bone; bone loss; bone mass; bone metabolism; breast cancer diagnosis; cancer recurrence; depression; effective therapy; experience; fitness; grasp; hormone therapy; improved; inflammatory marker; innovation; intervention effect; malignant breast neoplasm; programs; psychological outcomes; public health relevance; strength training; survivorship

DESCRIPTION (provided by applicant): Two thirds of all breast cancers diagnosed in US women express estrogen and/or progesterone receptors. Although 5 years of tamoxifen had long been the standard adjuvant hormonal therapy for women with early- stage, hormone receptor-positive breast cancer, the aromatase inhibitors (AI's) have rapidly supplanted tamoxifen as the hormonal therapy of choice. Several large adjuvant trials have demonstrated that using an AI in place of or after tamoxifen reduced the risk of breast cancer recurrence, as compared to treatment with 5 years of tamoxifen. A recent American Society of Clinical Oncology expert consensus panel recommended that all postmenopausal women with early-stage, hormone-receptor-positive breast cancer receive an AI as part of their adjuvant therapy. However, long term data regarding the safety and toxicity of AIs is largely lacking. Data from the large adjuvant trials evaluating the use of the AI's indicate that arthralgia is one of the major toxicities associated with AI therapy and one of the most common reasons for AI treatment discontinuation. There has been little data regarding effective treatments for arthralgias. In addition to arthralgia, other bone-related adverse effects of AI therapy include bone loss and fractures. Although medications such as bisphosphonates can be used to alleviate bone loss, these drugs also cause significant side effects. Given the efficacy of the AI's, it is essential that better ways to manage the toxicity of these agents be explored. Nonpharmacologic methods of managing the side effects of the AI's are especially desirable. Exercise has been shown to improve bone metabolism in healthy women, and to be beneficial for people with fibromyalgia, osteoarthritis and rheumatoid arthritis; however, no randomized trial has examined the impact of exercise on arthralgia or bone mass in breast cancer survivors taking AIs. In the proposed trial, we plan to evaluate the ability of a walking and strength training exercise program to attenuate side effects of AI therapy. Our trial will randomize 180 postmenopausal breast cancer patients, who have been taking an AI for at least 6 months and are currently experiencing at least mild arthralgia which started after initiating AI therapy, to a yearlong exercise intervention or to an attention control group. We will then examine the impact of exercise on severity of arthralgia, factors mediating the effect of exercise on arthralgia, and other side effects of AI therapy including endocrine-related quality of life and bone mineral density. Women will be randomized to a home- and gym-based exercise program or attention control (health education) group. Women randomized to exercise will participate in 150 min/wk of aerobic exercise and a twice-weekly strength training program. We will conduct baseline, 6- and 12-month clinic visits, as well as 3- and 9-month mailings to evaluate the effect of the intervention on study outcomes. Given the widespread use of the AI's, we believe that our approach is innovative and timely. If our intervention is able to alleviate AI-associated side effects and reduce the number of women who prematurely discontinue them, we believe that our study may prove beneficial for the large number of postmenopausal women diagnosed with hormone receptor-positive breast cancer each year. Our study will also be especially relevant to the mission of NCI and the Office of Cancer Survivorship to improve the quality of life for cancer survivors, support intervention survivorship research, and to ensure best practices for addressing the health needs of survivors. PUBLIC HEALTH RELEVANCE: A recent American Society of Clinical Oncology expert consensus panel recommended that all postmenopausal women with early-stage, hormone-receptor-positive breast cancer (~2/3 of all women diagnosed with breast cancer) receive an aromatase-inhibitor (AI) as part of their adjuvant therapy. Data from the large adjuvant trials evaluating the use of the AI's indicate that arthralgia and bone loss are the major toxicities associated with AI therapy and the most common reasons for AI treatment discontinuation. Our trial will examine the impact of an exercise program on alleviating AI-associated side effects such as arthralgia, bone mineral density, and endocrine-related quality of life, and may prove beneficial for the large number of postmenopausal women diagnosed with hormone receptor-positive breast cancer each year.

描述（由申请人提供）：美国女性诊断出的所有乳腺癌中，三分之二表达雌激素和/或孕激素受体。尽管 5 年他莫昔芬长期以来一直是早期激素受体阳性乳腺癌女性的标准辅助激素治疗，但芳香酶抑制剂 (AI) 已迅速取代他莫昔芬成为首选激素治疗。几项大型辅助试验表明，与 5 年他莫昔芬治疗相比，使用 AI 代替他莫昔芬或在他莫昔芬之后使用可以降低乳腺癌复发的风险。最近的美国临床肿瘤学会专家共识小组建议所有患有早期激素受体阳性乳腺癌的绝经后女性接受人工智能作为辅助治疗的一部分。然而，关于人工智能安全性和毒性的长期数据却很缺乏。评估 AI 使用情况的大型辅助试验的数据表明，关节痛是与 AI 治疗相关的主要毒性之一，也是停止 AI 治疗的最常见原因之一。关于关节痛有效治疗的数据很少。除了关节痛之外，人工智能治疗的其他与骨骼相关的副作用包括骨质流失和骨折。虽然双磷酸盐等药物可用于减轻骨质流失，但这些药物也会引起显着的副作用。鉴于人工智能的功效，有必要探索更好的方法来管理这些药物的毒性。控制人工智能副作用的非药物方法尤其值得期待。运动已被证明可以改善健康女性的骨代谢，并对纤维肌痛、骨关节炎和类风湿关节炎患者有益；然而，尚无随机试验研究运动对服用 AI 的乳腺癌幸存者的关节痛或骨量的影响。在拟议的试验中，我们计划评估步行和力量训练锻炼计划减轻人工智能疗法副作用的能力。我们的试验将把 180 名绝经后乳腺癌患者随机分配到为期一年的运动干预组或注意力对照组，这些患者已经服用 AI 至少 6 个月，目前正在经历至少轻度关节痛（在开始 AI 治疗后开始）。然后，我们将研究运动对关节痛严重程度的影响、介导运动对关节痛影响的因素，以及人工智能治疗的其他副作用，包括内分泌相关的生活质量和骨矿物质密度。女性将被随机分配到家庭和健身房锻炼计划或注意力控制（健康教育）组。随机参加运动的女性将参加每周 150 分钟的有氧运动和每周两次的力量训练计划。我们将进行基线、6 个月和 12 个月的临床就诊以及 3 个月和 9 个月的邮寄，以评估干预措施对研究结果的影响。鉴于人工智能的广泛使用，我们相信我们的方法是创新且及时的。如果我们的干预措施能够减轻人工智能相关的副作用并减少提前停止治疗的女性数量，我们相信我们的研究可能对每年诊断出患有激素受体阳性乳腺癌的大量绝经后女性有益。我们的研究还将与 NCI 和癌症幸存者办公室的使命特别相关，即改善癌症幸存者的生活质量、支持干预幸存者研究，并确保满足幸存者健康需求的最佳实践。公共健康相关性：最近的美国临床肿瘤学会专家共识小组建议所有患有早期激素受体阳性乳腺癌的绝经后女性（约占所有诊断出乳腺癌的女性的 2/3）接受芳香酶抑制剂（ AI）作为辅助治疗的一部分。评估 AI 使用情况的大型辅助试验的数据表明，关节痛和骨质流失是与 AI 治疗相关的主要毒性，也是 AI 治疗中止的最常见原因。我们的试验将研究运动计划对减轻人工智能相关副作用（如关节痛、骨矿物质密度和内分泌相关生活质量）的影响，并可能对大量被诊断为激素受体阳性的绝经后妇女有益每年都会患乳腺癌。