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.

项目概要/摘要 过去 40 年来，女性乳腺癌的总体年龄调整死亡率显着下降 年（1979 年的 31.5/100,000 人到 2016 年的 20.6/100,000），但是黑人女性的乳腺癌死亡率 仅略低于 20 世纪 70 年代（1979 年为 30.5/100,000，2016 年为 27.3/100,000）。 因为这些差异可能是多因素造成的，但身体成分的差异会改变肿瘤的暴露 传统上，化疗药物的剂量可能是影响因素之一。 使用体表面积 (BSA)，根据简单的身高和体重计算得出 然而，BSA 并未考虑去脂体重 (LBM) 和脂肪组织的差异。 (AT) 具有相同身高和体重的个体的 LBM 和 AT 分布可能显着不同， 这可能会导致药物分布、清除和药物相关毒性数据的变化。 大量基于人群的研究表明，在体重指数相似的女性中，平均而言，非 与非黑人相比，西班牙裔黑人的骨骼肌比例较高，而 AT 比例较低 西班牙裔白人身体成分的这些差异可能意味着使用标准化疗。 剂量（通过临床试验确定，通常主要是白人参与者）可能会导致许多 黑人女性每公斤 LBM 接受次优化疗剂量，增加了未能实现目标的风险 然而，仍有一些关键问题需要澄清。 在临床试验中评估基于身体成分的药物剂量变化之前，包括哪些 身体成分指标与最佳治疗结果以及剂量是否应集中相关 仅针对 LBM 或还包括肥胖措施，以实现我们改善乳腺癌的长期目标。 总体治疗结果并消除黑人女性治疗结果的差异，这项回顾性研究 400 名接受乳腺癌治疗的女性（约 44% 为白人，45% 为黑人）将使用现有的 计算机断层扫描用于测量身体成分并实现以下具体目标：1) 确定接受药物治疗的白人和黑人妇女之间每千克体重的药物剂量差异程度 针对浸润性乳腺癌的基于蒽环类或紫杉类的化疗方案，以及 2) 确定程度 药物剂量/kg LBM 和腹部 AT 测量独立且共同相关 化疗毒性和预定治疗的完成将有所贡献。 有关乳腺癌女性身体成分的重要基础数据，以及身体如何 如果发现身体成分测量与化疗有关，则成分可能因种族而异。 相关毒性，可以根据个人的身体成分调整药物剂量，以最大限度地发挥作用 治疗效果，同时最大限度地减少治疗相关的毒性。

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