Body composition and chemotherapy toxicity among women being treated for breast cancer

接受乳腺癌治疗的女性的身体成分和化疗毒性

• 批准号: 10406912
• 负责人: Kimberly Z Robien
• 金额: $ 21.92万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-18 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406912
• 关键词: Abdomen; Address; Adipose tissue; Age; Anthracycline; Black Populations; Black race; Blood Circulation; Body Composition; Body Surface Area; Body mass index; Body measure procedure; Breast; Breast Cancer Treatment; Cardiac Output; Cardiovascular system; Chemotherapy-Oncologic Procedure; Clinical Trials; Computer software; Data; Disease Progression; Disease remission; Dose; Dose-Limiting; Drug Kinetics; Evaluation; Exposure to; Failure; Fatty Liver; Female Breast Carcinoma; Foundations; Future; Glomerular Filtration Rate; Goals; Health; Height; Image; Individual; Measurement; Measures; Modeling; Muscle; Not Hispanic or Latino; Obesity; Outcome; Participant; Persons; Pharmaceutical Preparations; Population Study; Race; Recommendation; Recurrence; Reporting; Retrospective Studies; Risk; Roentgen Rays; Role; Scanning; Skeletal Muscle; Staging; Toxic effect; Toxicity due to chemotherapy; Treatment Effectiveness; Treatment Protocols; Treatment outcome; Treatment-related toxicity; Variant; Weight; Woman; X-Ray Computed Tomography; abdominal fat; base; black women; chemotherapeutic agent; chemotherapy; disparity elimination; dosage; drug clearance; drug distribution; high risk; improved; lean body mass; lipophilicity; malignant breast neoplasm; mortality; nutrition; obese person; optimal treatments; precision medicine; predictive modeling; simulation; taxane; tool; tumor

PROJECT SUMMARY/ABSTRACT Overall age-adjusted mortality rates for female breast cancer have decreased significantly over the last 40 years (31.5/100,000 in 1979 to 20.6/100,000 in 2016), however breast cancer mortality rates for Black women are only slightly lower than they were in the 1970s (30.5/100,000 in 1979 vs. 27.3/100,000 in 2016). Reasons for these disparities are likely multifactorial, but differences in body composition that alter the tumor’s exposure to chemotherapy drugs may be one contributing factor. Traditionally, chemotherapy doses have been calculated using body surface area (BSA), which is calculated based on simple height and weight measurements. However, BSA does not account for differences in lean body mass (LBM) and adipose tissue (AT). Individuals with the same height and weight can have significantly different distributions of LBM and AT, which could contribute to variation in drug distribution, clearance, and drug-related toxicity. Data from several large population-based studies indicate that among women with similar body mass index, on average, non- Hispanic Blacks have a higher proportion of skeletal muscle and lower proportion of AT compared to non- Hispanic Whites. These differences in body composition could mean that use of standard chemotherapy dosages (established through clinical trials with often predominantly White participants) could result in many Black women receiving sub-optimal chemotherapy dosing per kg LBM, increasing the risk of failure to achieve remission, disease progression or recurrence. However, there are still key questions that need to be clarified before changes in drug dosing based on body composition can be evaluated in clinical trials, including which body composition metrics are associated with optimal treatment outcomes, and whether dosing should focus solely on LBM or also include measures of adiposity. To address our long-term goal of improving breast cancer treatment outcomes overall and eliminating disparities in outcomes for Black women, this retrospective study of 400 women who were treated for breast cancer (approximately 44% White and 45% Black) will use existing computed tomography scans to measure body composition and address the following specific aims: 1) determine the extent to which drug dose/kg LBM differs between White and Black women being treated with an anthracycline- or taxane-based chemotherapy regimen for invasive breast cancer, and 2) determine the extent to which drug dose/kg LBM and measures of abdominal AT are independently and jointly associated with chemotherapy toxicity and completion of scheduled treatment. Findings from the proposed study will contribute important foundational data on body composition among women with breast cancer, and how body composition may vary by race. If body composition measures are found to be associated with chemotherapy- related toxicity, drug dosing could be tailored to an individual’s body composition in order to maximize treatment effectiveness while minimizing treatment-related toxicity.

项目摘要/摘要 在过去的40个 年（1979年31.5/100,000，2016年的20.6/100,000），但是黑人妇女的乳腺癌死亡率 仅比1970年代的略低（1979年为30.5/100,000，2016年27.3/100,000）。原因 因为这些分布可能是多因素的，但是身体成分的差异会改变肿瘤的暴露 化学疗法药物可能是一个因素之一。传统上，化学疗法剂量一直是 使用身体表面积（BSA）计算，该面积是根据简单的高度和体重计算的 测量。但是，BSA不考虑瘦体重（LBM）和脂肪组织的差异 （在）。高度和体重相同的个体可以具有LBM和AT分布的显着不同 这可能导致药物分布，清除和与药物有关的毒性的变化。来自几个的数据 大型基于人群的研究表明，在平均而言，体重指数相似的女性中 西班牙裔黑人比非 - 西班牙裔白人。人体组成的这些差异可能意味着使用标准化疗 剂量（通过通常主要是白人参与者的临床试验建立）可能导致许多 黑人妇女每公斤lbm接受以下化学疗法的剂量，增加了未能达到的风险 缓解，疾病进展或复发。但是，仍然有一些关键问题需要澄清 在临床试验中可以评估基于身体成分的药物给药之前，包括 身体成分指标与最佳治疗结果以及剂量是否应集中 仅在LBM上或包括肥胖度量。解决我们改善乳腺癌的长期目标 总体治疗结果并消除了黑人妇女的预后差异，这项回顾性研究 接受乳腺癌治疗的400名女性（大约44％的白色和45％黑色）将使用现有 计算机断层扫描以测量身体成分并解决以下特定目的：1） 确定药物剂量/kg lbm在用a的白人和黑人妇女之间有所不同 针对侵入性乳腺癌的蒽环类药物或基于紫杉烷的化学疗法方案，2）确定程度 药物剂量/kg lbm和腹部AT的措施与 化学疗法毒性和预定治疗的完成。拟议研究的发现将有助于 关于乳腺癌女性身体组成的重要基础数据，身体如何 构图可能因种族而异。如果发现身体成分与化学疗法有关 相关的毒性，药物剂量可以量身定制为个人的身体成分，以最大化 治疗有效性，同时最小化治疗相关的毒性。

项目成果

Body composition and chemotherapy toxicity among women treated for breast cancer: a systematic review.

接受乳腺癌治疗的女性的身体成分和化疗毒性：系统评价。

• DOI: 10.1007/s11764-023-01380-7
• 发表时间: 2023
• 期刊: Journal of cancer survivorship : research and practice
• 作者: Wopat,Heather;Harrod,Tom;Brem,RachelF;Kaltman,Rebecca;Anderson,Kendall;Robien,Kim
• 通讯作者: Robien,Kim