(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）：与最有利的乳腺癌结果相关的最佳体型尚未确定。最重要的是，并非所有超重和肥胖的女性出现不良后果的风险都较高。肌肉质量 (MM) 对体内内分泌、免疫和荷尔蒙产生强大的影响。少肌症（低肌肉量或肌肉萎缩）和少肌性肥胖症（即肥胖和低肌肉量）在乳腺癌幸存者中很常见，并且可能因增加脂肪量和减少肌肉量的肿瘤治疗而进一步加剧。针对 PQ2， “肥胖如何与癌症风险相关”，我们建议除了单独的肥胖或脂肪量 (FM) 之外，还研究 MM 的影响以及肥胖与肌肉发达的关系这将进一步我们对与最佳预后相关的理想身体成分的理解，并可能有助于解释超重和（轻度）肥胖预测乳腺癌风险升高的观察结果，但矛盾的是并不总是预测诊断后死亡率更高。最近，开发并验证了使用腹部计算机断层扫描 (CT) 扫描测量 FM 和 MM 的方法，以识别两组女性（总​​计 n=3,250）。 2000 年至 2015 年间在北加州凯撒医疗机构 (KPNC) 和达纳法伯癌症研究所 (DCFI) 诊断出患有 I-III 期浸润性乳腺癌的患者，我们将使用收集的 CT 扫描作为诊断时常规护理的一部分，并评估 FM 和MM 旨在了解身体成分、肌肉减少症和肌肉减少症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。具体来说，我们将检查诊断时乳腺癌幸存者的肌肉萎缩（少肌症）和少肌症肥胖水平，以及其如何随重要的医学和人口特征而变化（目标 1）。我们还将研究 FM、MM、肌少症、肌少症肥胖和心脏代谢危险因素之间的关联（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个大规模调查，旨在检查身体成分在诊断时和治疗前对乳腺癌结果的影响。这项研究使用一种新颖、最先进的工具来测量脂肪/肌肉质量，该工具在生物学上比身高和体重的标准测量更相关，并且可以提供有关身体成分在癌症生存中的作用的重要见解。这项研究具有产生巨大影响的潜力，因为作为常规护理的一部分已经收集的 CT 扫描可用于评估脂肪和肌肉质量，而几乎不增加额外成本。或者，其他方法，包括双能 X 射线吸收测定法 (DXA) 扫描或生物电阻抗分析 (BIA) 也可应用于临床实践，为 BMI 添加重要的生理测量，以帮助有针对性和个性化的体重控制策略和其他治疗方法，以预防肌肉萎缩。质量损失，提高生存率。 FM 和 MM 在乳腺癌预后中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。