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.

项目总结/摘要 在过去的40年里，女性乳腺癌的年龄调整死亡率显著下降。 年（1979年为31.5/100，000，2016年为20.6/100，000），但黑人妇女的乳腺癌死亡率 仅略低于20世纪70年代（1979年为30.5/10万，2016年为27.3/10万）。原因 因为这些差异可能是多因素的，但身体成分的差异改变了肿瘤的暴露， 化疗药物可能是一个促成因素。传统上，化疗剂量 使用体表面积（BSA）计算，BSA基于简单的身高和体重计算 测量.然而，BSA不能解释瘦体重（LBM）和脂肪组织的差异 （AT）。具有相同身高和体重的个体可以具有显著不同的LBM和AT分布， 这可能导致药物分布、清除和药物相关毒性的变化。数据来自几个 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， 西班牙裔黑人与非西班牙裔黑人相比，骨骼肌比例较高，AT比例较低。 西班牙白人这些身体成分的差异可能意味着使用标准化疗 剂量（通过临床试验建立，通常主要是白色参与者）可能会导致许多 黑人女性接受每公斤LBM次优化疗剂量，增加了未能实现的风险 缓解、疾病进展或复发。然而，仍有关键问题需要澄清 在基于身体组成的药物剂量变化可以在临床试验中进行评估之前， 身体成分指标与最佳治疗结果相关，以及剂量是否应关注 或者也包括肥胖的测量。为了实现我们改善乳腺癌的长期目标， 治疗结果的整体和消除黑人妇女的结果差异，这项回顾性研究， 400名接受乳腺癌治疗的女性（约44%白色和45%黑人）将使用现有的 计算机断层扫描测量身体成分，并解决以下具体目标：1） 确定接受药物治疗的白色和黑人女性之间药物剂量/kg LBM的差异程度 蒽环类或紫杉烷为基础的化疗方案用于浸润性乳腺癌，和2）确定程度 其中药物剂量/kg LBM和腹部AT的测量值独立和联合与 化疗毒性和完成预定治疗。拟议研究的结果将有助于 乳腺癌患者身体组成的重要基础数据，以及身体如何 组成可能因种族而异。如果发现身体成分与化疗有关- 相关的毒性，药物剂量可以根据个体的身体组成进行调整，以最大限度地提高 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