(PQA2) Exploring the role of sarcopenia in obesity and breast cancer survival

(PQA2) 探索肌肉减少症在肥胖和乳腺癌生存中的作用

基本信息

批准号：
9320716
负责人：
BETTE J CAAN
金额：
$ 60.79万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9320716
关键词：
Abdomen Address Adopted Affect Age Aging Biolectric Impedance Biological Blood Pressure Body Composition Body Size Body fat Body mass index Body measure procedure Breast Cancer survivor California Cancer Patient Cancer Prognosis Cardiovascular Diseases Caring Catabolism Cessation of life Characteristics Cholesterol Chronic Chronic Disease Comorbidity Complex Cox Models Dana-Farber Cancer Institute Data Diabetes Mellitus Diagnosis Disease Dual-Energy X-Ray Absorptiometry Endocrine Ethnic Origin Fatty acid glycerol esters General Population Glucose HDL-triglyceride Height High Risk Woman Hormonal Hospitalization Immune Incidence Individual Inflammation Insulin Resistance Intervention Investigation Kidney Diseases Lead Linear Regressions Lipids Logistic Regressions Malignant Neoplasms Measures Medical Meta-Analysis Metabolic Methods Mild obesity Modeling Molecular Muscle Muscular Atrophy Newly Diagnosed Obesity Outcome Overweight Pathway interactions Persons Physical activity Physiological Population Prognostic Factor Proteins Reporting Research Risk Risk Factors Role Scanning Survivors Treatment-related toxicity Underweight Variant Weight Weight maintenance regimen Woman X-Ray Computed Tomography breast cancer diagnosis breast cancer survival cancer risk cancer survival cardiometabolic risk clinical care clinical practice cohort cost cost efficient design disorder risk functional status improved individualized medicine insight malignant breast neoplasm mortality muscle form novel obesity risk outcome forecast prevent public health relevance reduced muscle mass response routine care routine practice sarcopenia sarcopenic obesity standard measure tool treatment strategy tumor progression

项目摘要

DESCRIPTION (provided by applicant): The optimal body size associated with the most favorable breast cancer outcomes is not well established. Most importantly, not all overweight and obese women are at higher risk of poor outcomes. Muscle mass (MM) exerts powerful endocrine, immune, and hormonal influences within the body. Sarcopenia (low muscle mass or muscle wasting) and sarcopenic obesity" (i.e., obesity and low muscle mass) are common in breast cancer survivors and may be further exacerbated by oncological treatments which increase fat mass and reduce muscle mass. In response to PQ2, "How does obesity relate to cancer risk", we propose to examine in addition to adiposity or fat mass (FM) alone, the effect of MM and the relationship of adiposity to muscularity on breast cancer outcomes. This will further our understanding of the ideal body composition associated with the best prognosis and may help explain the observation that overweight and (mild) obesity predict elevated risk of breast cancer, but paradoxically do not always predict higher mortality after diagnosis compared with those who are normal-weight or underweight. Recently, methods to measure FM and MM using abdominal Computerized Tomography (CT) scans have been developed and validated to identify individuals with sarcopenia. In two cohorts of women (total n=3,250) diagnosed between 2000 and 2015 with Stage I-III invasive breast cancer at the Kaiser Permanente Northern California (KPNC) and the Dana Farber Cancer Institute (DCFI), we will use CT scans collected as part of routine care at diagnosis, and assess FM and MM in order to understand the role of body composition, sarcopenia, and sarcopenic obesity in breast cancer prognosis in an attempt to explain how obesity relates to survival risk. Specifically, we will examine the level of muscle wasting (sarcopenia) and sarcopenic obesity in breast cancer survivors at diagnosis and how that varies by important medical and demographic characteristics (Aim 1). We will also examine associations between FM, MM, sarcopenia, sarcopenic obesity, and cardiometabolic risk factors (Aim 2); chemotoxicity (Aim 3); and breast cancer-specific and overall mortality (Aim 4). Multiple linear and logistic regression will be used to evaluate most associations, and Cox models will be used to evaluate associations with mortality. The proposed study is the first large-scale investigation to examine the role of body composition at diagnosis and before treatment on breast cancer outcomes. This study uses a novel, state-of-the art tool to measure fat/muscle mass that is biologically more relevant than standard measures of height and weight, and could provide important insight into the role of body composition in cancer survival. This study has the potential for high impact since CT scans already collected as a part of regular care could be used to assess fat and muscle mass with little added extra cost. Alternatively, other methods including dual energy X-ray absorptiometry (DXA) scans or bioelectrical impedance analyses (BIA) could be adopted into clinical practice, adding an important physiologic measure to BMI to help target and personalize weight control strategies and other treatments to prevent muscle mass loss, and improve survival. Both FM and MM have independent metabolic roles in breast cancer prognosis that may ultimately help to explain the mechanistic pathways underlying the association between obesity and breast cancer survival.

描述（由申请人提供）：与最有利的乳腺癌结局相关的最佳体型尚未确定。最重要的是，并非全部超重和肥胖的妇女面临不良结果的风险更高。肌肉质量（MM）在体内发挥强大的内分泌，免疫和激素影响。肌肉减少症（肌肉质量低或肌肉浪费）和肌肉减少性肥胖”（即肥胖和低肌肉质量）在乳腺癌幸存者中很常见，并且可能会进一步加剧肿瘤治疗，从而通过增加脂肪质量并减少肌肉质量的肿瘤治疗，从而减少对PQ2的响应。肥胖与乳腺癌结局的关系将进一步了解与最佳预后相关的理想身体成分，并有助于观察到，超重和（轻度）肥胖症可以预测乳腺癌的风险升高，但矛盾的是，与近期计算机的相比，与较高的诊断相比，毒性并不总是预测较高的诊断后的死亡率。经过开发和验证，以确定在2000年至2015年间诊断出的两名妇女（总数n = 3,250）中，在Kaiser Northerente北加州（KPNC）（KPNC）的I-II-III型入侵性乳腺癌之间进行了诊断。乳腺癌预后中的身体成分，肌肉减少症和肌肉减少性肥胖，以解释肥胖与生存风险的关系。具体而言，我们将检查诊断时乳腺癌幸存者中肌肉浪费水平（肌肉减少症）和肌肉减少症的水平，以及这如何随重要的医学和人口统计学特征而变化（AIM 1）。我们还将研究FM，MM，肌肉减少症，肌肉减少肥胖和心脏代谢危险因素之间的关联（AIM 2）；化学毒性（AIM 3）；以及乳腺癌特异性和总体死亡率（AIM 4）。多个线性和逻辑回归将用于评估大多数关联，COX模型将用于评估与死亡率的关联。拟议的研究是首次研究身体成分在诊断和治疗前对乳腺癌预后的作用的大规模研究。这项研究使用一种新颖的，最先进的工具来测量比标准身高和体重的标准度量在生物学上更相关的脂肪/肌肉质量，并且可以为人体成分在癌症生存中的作用提供重要的见解。这项研究具有高影响力的潜力，因为CT扫描已经作为常规护理的一部分收集，可用于评估脂肪和肌肉质量，而几乎没有增加额外的成本。另外，可以将包括双能X射线吸收仪（DXA）扫描或生物电性阻抗分析（BIA）在内的其他方法采用到临床实践中，从而向BMI增加一项重要的生理指标，以帮助靶向目标和个性化加重控制策略和其他治疗，以防止肌肉质量损失，并提高肌肉质量损失，并提高存活率。 FM和MM在乳腺癌预后中均具有独立的代谢作用，最终可能有助于解释肥胖与乳腺癌生存之间关联的机械途径。