The Women In Steady Exercise Research (WISER) SurwVor Trial

乳腺癌幸存者面临双重挑战：1)复发的风险；2)处理治疗的长期后遗症。面对这些挑战可能是沉重的负担，导致生活质量下降。肥胖和久坐不动的生活方式使这些问题变得更加复杂。WISER Survivor试验的目标是评估运动和/或通过限制卡路里减肥对常见的长期治疗副作用(淋巴水肿)、复发的生物标志物和生活质量的影响。 淋巴水肿是一种慢性、进行性、无法治愈的疾病，其特征是手臂肿胀，功能和外观出现阴性变化，以及令人烦恼的症状。它是更常见、更昂贵、更令人担心的乳腺癌治疗持续不良影响之一。在我们完成的工作中，每周两次举重将需要医疗护理的临床淋巴水肿事件的数量减少了一半。在建议的WISER Survivor试验中，我们试图评估是否在举重干预的基础上增加有氧运动或通过限制热量减肥来进一步改善淋巴水肿的临床结果。 WISER幸存者试验还将测试锻炼和减肥干预对相同复发生物标志物的影响，并在小鼠模型研究中进行测试(项目1)。生物标志物包括性激素、炎症标志物、生长因子、脂肪因子和氧化应激。这两个配对项目的创新包括在复发环境中评估这些干预措施的效果的新方法，以及在小鼠和人类中比较同等干预措施对生物标记物的影响。此外，我们还评估了能量平衡干预对一种与致病血管生成相关的新生物标志物的影响。另一项创新包括一个独特的机会，可以评估这些生物标志物中的任何一个的变化是否与临床淋巴水肿结果相关。最后，我们试图评估我们的干预措施对患有淋巴水肿的乳腺癌幸存者的生活质量的影响。 因此，我们提出了一项为期一年的随机对照减肥和运动干预试验，对象是多民族的烤箱/蔬菜和肥胖的绝经后乳腺癌幸存者，他们都有临床确诊的淋巴水肿。本次试验分为四组：单纯运动组、单纯减肥组、运动与减肥相结合组和对照组，每组样本量为125个(总N=500)。

Breast cancer survivors face dual challenges: 1) risk of recurrent disease and 2) dealing with the long term sequelae of their treatments. Facing these challenges can be burdensome, resulting in reduced quality of life. Obesity and sedentary lifestyle further complicate these issues. The goal ofthe WISER Survivor trial is to assess the effects of exercise and/or weight loss through caloric restriction on a common long term adverse effect of treatment (lymphedema), biomarkers for recurrence, and quality of life. Lymphedema is a chronic, progressive, incurable condition characterized by arm swelling and negative alterations in function and appearance, as well as bothersome symptoms. It is among the more common, expensive, and feared persistent adverse breast cancer treatment effects. In our completed work, twice weekly weight-lifting reduced by half the number of incident clinical lymphedema events requiring medical care. In the proposed WISER Survivor trial we seek to assess whether adding aerobic exercise or weight loss through caloric restriction to the weight-lifting intervention further improves lymphedema clinical outcomes. The WISER Survivor Trial will also test the effects ofthe exercise and weight loss interventions on the same recurrence biomarkers to be tested in the mouse model study (Project 1). The biomarkers include sex hormones, markers of inflammation, growth factors, adipokines, and oxidative stress. The innovation of these two paired projects include the novel approach of assessing effects of these interventions in the recurrence setting, as well as comparing effects on biomarkers in equivalent interventions in mice and humans. In addition, we assess effects of our energy balance interventions on a novel biomarker related to pathogenic angiogenesis. Another innovation includes a unique opportunity to assess whether changes in any of these biomarkers are correlated with clinical lymphedema outcomes. Finally, we seek to assess effects of our interventions on quality of life in breast cancer survivors with lymphedema. Therefore, we propose a one year randomized controlled weight loss and exercise intervention trial in a multi-ethnic cohort of oven/veight and obese post-menopausal breast cancer survivors with clinically confirmed lymphedema. There will be four groups in this trial: exercise only, weight loss only, exercise and weight-loss combined, and a control group, with a sample size of 125 per group (total N=500).