(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

• 批准号: 9081551
• 负责人: BETTE J CAAN
• 金额: $ 60.25万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9081551
• 关键词: Abdomen; Accounting; Address; Adopted; Affect; Age; Aging; Biolectric Impedance; Blood Pressure; Body Composition; Body Size; Body fat; Body mass index; Breast Cancer Patient; Breast Cancer survivor; California; 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; Diagnostic Neoplasm Staging; Disease; Dual-Energy X-Ray Absorptiometry; Endocrine; Ethnic Origin; Fatty acid glycerol esters; General Population; Glucose; HDL-triglyceride; Health; Height; High Risk Woman; Hormonal; Hospitalization; Immune; Incidence; Individual; Inflammation; Insulin Resistance; Intervention; Investigation; Kidney Diseases; Lead; Linear Regressions; Lipids; Logistic Regressions; Malignant Neoplasms; Mass in breast; Measures; Medical; Meta-Analysis; Metabolic; Methods; Mild obesity; Modeling; Molecular; Muscular Atrophy; Newly Diagnosed; Obesity; Outcome; Overweight; Pathway interactions; Persons; Physical activity; Physiological; Population; Prognostic Factor; Proteins; Reporting; Research; Risk; Risk Factors; Role; Scanning; Staging; 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; outcome forecast; prevent; reduced muscle mass; response; routine care; sarcopenia; sarcopenic obesity; standard measure; tool; treatment strategy; tumor progression

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）：与最有利的乳腺癌预后相关的最佳体型尚未得到很好的确定。最重要的是，并非所有超重和肥胖的女性都有更高的不良后果风险。肌肉质量（MM）在体内具有强大的内分泌、免疫和激素影响。肌少症（低肌肉量或肌肉萎缩）和肌少性肥胖（即肥胖和低肌肉量）在乳腺癌幸存者中很常见，并可能因肿瘤治疗增加脂肪量和减少肌肉量而进一步恶化。针对PQ2“肥胖与癌症风险之间的关系”，我们建议在肥胖或脂肪量（FM）单独的基础上，研究MM的影响以及肥胖与肌肉量的关系对乳腺癌预后的影响。这将进一步加深我们对与最佳预后相关的理想身体组成的理解，并有助于解释超重和（轻度）肥胖预测乳腺癌风险增加的观察结果，但矛盾的是，与正常体重或体重不足的人相比，诊断后并不总是预测更高的死亡率。最近，使用腹部计算机断层扫描（CT）测量FM和MM的方法已经开发并验证了识别肌肉减少症患者的方法。在2000年至2015年期间在北加州Kaiser Permanente （KPNC）和Dana Farber癌症研究所（DCFI）诊断为I-III期浸润性乳腺癌的两组女性（总n= 3250）中，我们将使用CT扫描作为诊断时常规护理的一部分，并评估FM和MM，以了解身体成分、肌肉减少症和肌肉减少性肥胖在乳腺癌预后中的作用，试图解释肥胖与生存风险的关系。具体而言，我们将研究乳腺癌幸存者在诊断时的肌肉萎缩（肌肉减少症）和肌肉减少性肥胖水平，以及它们如何因重要的医学和人口统计学特征而变化（目的1）。我们还将研究FM、MM、肌肉减少症、肌肉减少性肥胖和心脏代谢危险因素之间的关系（目标2）；化学毒性（目标3）；乳腺癌特异性死亡率和总体死亡率（目标4）。多元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。这项拟议的研究是第一次大规模调查身体成分在诊断和治疗前对乳腺癌结果的作用。这项研究使用了一种新颖的、最先进的工具来测量脂肪/肌肉质量，这在生物学上比标准的身高和体重测量更相关，并且可以为身体成分在癌症生存中的作用提供重要的见解。这项研究具有很大的潜在影响，因为CT扫描已经作为常规护理的一部分收集，可以用来评估脂肪和肌肉质量，几乎没有额外的费用。也可以将双能x线吸收仪（DXA）扫描或生物电阻抗分析（BIA）等其他方法应用于临床实践，为BMI增加一项重要的生理指标，以帮助制定和个性化体重控制策略和其他治疗，防止肌肉质量下降，提高生存率。FM和MM在乳腺癌预后中都具有独立的代谢作用，这可能最终有助于解释肥胖与乳腺癌生存之间关联的机制途径。