Every Day Counts: A lifestyle program for women metastatic breast cancer

每一天都很重要：针对女性转移性乳腺癌的生活​​方式计划

• 批准号: 10366559
• 负责人: Patricia Maureen Sheean
• 金额: $ 68.21万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366559
• 关键词: Address; Adherence; Adipose tissue; Adopted; Adverse event; African American; American Cancer Society; Behavior; Behavioral; Biological; Biological Markers; Body Composition; Cancer Survivor; Caring; Chronic Disease; Clinical; Communities; Consensus; Control Groups; Disease; Disease Management; Distress; Eating; Evidence based intervention; Exercise; Exhibits; Fatigue; Feedback; Goals; Guidelines; Habits; Incidence; Inflammation; Inflammatory; Insulin Resistance; Intervention; Intervention Trial; Lead; Life Style; Mediating; Menopausal Status; Metastatic breast cancer; Methodology; MicroRNAs; Mitochondria; Molecular; Obesity; Outcome; Participant; Pathway interactions; Patient Outcomes Assessments; Physical Function; Physical activity; Pilot Projects; Prognosis; Program Sustainability; Quality of life; Randomized; Recommendation; Research; Safety; Serum; Survivors; Symptoms; Testing; Thinness; Toxicity due to chemotherapy; Treatment-related toxicity; Underserved Population; Update; Waiting Lists; Woman; Work; adipokines; attentional control; base; clinically significant; control trial; differential expression; efficacy evaluation; exercise intervention; experience; healthy lifestyle; improved; innovation; insulin sensitivity; interest; intervention effect; lifestyle intervention; multidisciplinary; novel; nutrition; physiologic model; pilot trial; post intervention; prognosis biomarker; prognostic; prognostic of survival; programs; recruit; reduce symptoms; survivorship; symptom management; targeted treatment; therapy design; treatment response; trend; tumor progression; young woman

The community of women with metastatic breast cancer (MBC) is growing due to greater disease incidence and treatment advances, with over 30% of women now surviving over 5 years (vs. just 4% in 2000). Managing symptoms to maintain the highest quality of life (QOL) is the major goal of care in the metastatic setting. Thus, research that addresses QOL, prognosis and survivorship in this burgeoning and underserved survivor group is critically needed. BC treatment is associated with adverse body composition changes, specifically gains in adipose tissue and reductions in strength and lean mass (LM). Excess adiposity contributes to inflammation and insulin-resistance, which are theorized to promote tumor progression and loss of LM. Low levels of LM are associated with chemotherapy toxicity, increased symptom burden and compromised survival in women with MBC. Lifestyle interventions with early stage BC survivors result in reduced symptoms, improved biomarkers of BC prognosis and enhanced quality of life (QOL). To date, women with MBC have been largely excluded from these trials. Our pilot work in women with MBC demonstrates they are interested, capable, adherent and benefit from participation in a lifestyle intervention. Our results show clinically meaningful improvements in QOL, increased physical activity and strength. We also find improved trends in biomarkers of prognosis, as well as mitochondrial function for women in the immediate intervention vs. control group. Further, our work shows that inflammation-associated microRNAs are differentially expressed following participation in our pilot trial, providing highly novel potential targets to explain mechanisms by which lifestyle interventions improve QOL for these women. We propose a randomized atttention control trial in women with MBC (n=176) to test the immediate and sustained effects of “Every Day Counts,” a 16-week lifestyle intervention based on current lifestyle recommendations for cancer survivors. This trial is adequately powered to examine changes in: 1) QOL - the primary determinant of care in the metastatic setting and (2) body composition, serum biomarkers of prognosis/survival, and pertinent patient reported outcomes. We will also explore mitochondrial function and novel microRNA signatures associated with inflammatory biomarkers and mitochondrial function. Every Day Counts incorporates critical feedback and experiences from our pilot study with women with MBC. Our robust, multidisciplinary study team applies an innovative, highly integrated physiologic model to examine the mechanistic effects of the intervention on decidedly relevant outcomes of interest. The present study challenges current clinical assumptions regarding the presumed ineffectiveness of lifestyle behaviors in the metastatic setting, providing evidence that may inform a paradigm shift expanding the application and relevance of the nutrition and physical activity guidelines to women with MBC. Importantly, this study will provide clinicians with updated evidence and strategies to help make every day count for women with MBC representing high impact for a currently underserved group of survivors.

转移性乳腺癌（MBC）的妇女社区正在增长，由于更大的疾病发病率 随着治疗的进步，现在超过30%的妇女存活超过5年（2000年仅为4%）。管理 症状，以维持最高的生活质量（QOL）是转移性环境中护理的主要目标。因此，在本发明中， 针对这一新兴且服务不足的幸存者群体的生活质量、预后和生存率的研究 是非常需要的。BC治疗与不良的身体成分变化有关，特别是在 脂肪组织和减少力量和瘦体重（LM）。过度肥胖导致炎症 和胰岛素抵抗，理论上它们促进肿瘤进展和LM的丧失。低水平的LM 与化疗毒性、症状负担增加和女性生存率降低相关， MBC。对早期BC幸存者的生活方式干预可减轻症状，改善生物标志物 BC预后和提高生活质量（QOL）。迄今为止，患有MBC的妇女基本上被排除在 这些审判。我们在MBC妇女中的试点工作表明，她们对MBC感兴趣，有能力，坚持， 从参与生活方式干预中获益。我们的研究结果显示， QOL，增加体力活动和力量。我们还发现预后生物标志物的改善趋势， 以及直接干预组与对照组妇女的线粒体功能。此外，我们的工作 显示炎症相关的microRNAs在参与我们的试验后差异表达， 试验，提供了高度新颖的潜在目标，以解释生活方式干预改善的机制 这些女性的QOL。我们提出了一项在MBC妇女中进行的随机注意力对照试验（n=176）， “每一天都很重要”的即时和持续效果，这是一项基于当前生活方式的16周生活方式干预， 癌症幸存者的生活方式建议本试验有足够的把握度检查以下方面的变化：1） QOL -转移性环境中护理的主要决定因素和（2）身体组成， 预后/存活率和相关患者报告的结果。我们还将探索线粒体功能， 与炎症生物标志物和线粒体功能相关的新型microRNA特征。每天 计数结合了关键的反馈和经验，从我们的试点研究与妇女与MBC。我们强大的， 多学科研究小组应用创新的，高度集成的生理模型来检查 干预对明确相关的关注结果的机械效应。本研究 挑战了目前临床上关于生活方式行为无效的假设， 转移性环境，提供证据，可能会告知范式转变，扩大应用， 营养和身体活动指南与MBC女性的相关性。重要的是，这项研究将 为临床医生提供最新的证据和策略，帮助MBC女性度过每一天 这对目前得不到充分服务的幸存者群体具有重大影响。