Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors

通过运动来治疗与肥胖相关的慢性炎症有可能改善肥胖症的预后 绝经后乳腺癌幸存者。肥胖被认为是乳房的主要可改变因素 全球癌症死亡率与复发增加和总存活率下降有关 费率。肥胖刺激癌症进展的一个中心机制是通过慢性、低级别 脂肪组织中的炎症。特别是，白色脂肪组织(WAT)是一个代谢复杂的器官 由能够分泌脂肪因子和与之相关的促炎细胞因子的脂肪细胞组成 肿瘤发生学。WAT的慢性炎症包括脂肪组织巨噬细胞(ATM)的积聚。 具体地说，ATM M1的表型随着肥胖而升高，提供了丰富的细胞因子来源，这些细胞因子是关键 肥胖相关的胰岛素抵抗的介体。脂肪质量的增加和精瘦质量的下降，称为 骨质源性肥胖，被观察到是治疗的副作用，进一步促进了肥胖症的发展 以及随后M1表达的升高。有利的是，运动引起的骨骼肥胖症的变化会导致 M1自动取款机的减少，以及M2自动取款机的增加，已知的是通过减弱胰岛素抵抗来预防胰岛素抵抗 发炎。然而，目前尚不清楚这可能会对癌症预后产生什么影响，以及 运动在减少慢性炎症方面最有效。我们的一般假设是，练习设计成 针对慢性炎症和相关的纤维性肥胖将改善肥胖症的预后 绝经后乳腺癌幸存者。我们提出了一项第二阶段随机对照试验，以比较两种联合治疗的效果 早期肥胖者有氧运动和阻力运动干预与注意对照组的比较 已完成初级癌症治疗的绝经后乳腺癌幸存者。这项提议将 解决以下目标：1)确定运动对肥胖相关慢性炎症的影响；2) 检查运动对肌肉源性肥胖的影响；3)确定运动对乳腺癌的影响 并评估慢性炎症减轻是否与乳腺癌有关 预后。这项研究具有创新性，因为a)我们将针对脂肪组织炎症生物标记物 改善癌症预后，b)推导出使用可测量的炎症标志物的数学模型 为了预测预后，c)利用一种新的活组织检查方法获取腹部深部皮下脂肪组织，以 解决机制预测问题，以及d)采用独特的阶段化、循环式练习设计 减少慢性炎症。如果目标实现，这项研究的发现将产生新的知识 关于乳腺癌幸存者最有可能改善预后的锻炼指南。 好了！

Targeting chronic inflammation related to obesity with exercise has the potential to improve prognosis in obese postmenopausal breast cancer survivors. Obesity is considered a leading modifiable contributor to breast cancer mortality worldwide due to its association with increased recurrence and decreased overall survival rate. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. In particular, white adipose tissue (WAT) is a metabolically complex organ comprised of adipocytes capable of secreting adipokines and proinflammatory cytokines related to tumorigenesis. Chronic inflammation of WAT includes accumulation of adipose tissue macrophages (ATMs). Specifically, the ATM M1 phenotype, elevated with obesity, provides a rich source of cytokines, which are key mediators of obesity-associated insulin resistance. Gains in fat mass and a decline in lean mass, known as sarcopenic obesity, are observed as a treatment side effect, further contributing to the development of WAT and subsequent elevated M1 expression. Favorably, exercise-induced changes in sarcopenic obesity lead to a reduction in M1 ATMs, and increase in M2 ATMs known to protect against insulin resistance by attenuating inflammation. However it is unknown what impact this may have on cancer prognosis and what forms of exercise are most effective at reducing chronic inflammation. Our general hypothesis is that exercise designed to target chronic inflammation and associated sarcopenic obesity will improve prognosis in obese postmenopausal breast cancer survivors. We propose a Phase II RCT to compare the effects of two combined aerobic and resistance exercise interventions relative to an attention control group among early-stage obese postmenopausal breast cancer survivors who have completed primary cancer therapy. This proposal will address the following aims: 1) determine the effects of exercise on obesity-associated chronic inflammation; 2) examine the effects of exercise on sarcopenic obesity; 3) determine the effects of exercise on breast cancer prognosis and to assess whether reductions in chronic inflammation are associated with breast cancer prognosis. This study is innovative because a) we will target adipose tissue inflammatory biomarkers to improve cancer prognosis, b) derive a mathematical model that employs measureable markers of inflammation to predict prognosis, c) utilize a novel biopsy method to obtain deep subcutaneous abdominal adipose tissue to address a mechanistic prognostic question, and d) employ a unique periodized, circuit-style exercise design to reduce chronic inflammation. If the aims are achieved, findings from this study will generate new knowledge about exercise guidelines for breast cancer survivors most likely to improve prognosis. !