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

项目摘要/摘要 在过去的40年里，女性乳腺癌的总体年龄调整死亡率显著下降。 多年来(1979年为31.5/10万，2016年为20.6/10万)，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，但改变肿瘤暴露的身体成分的差异 对化疗药物的依赖可能是一个促成因素。传统上，化疗剂量一直是 使用身体表面积(BSA)计算，BSA是根据简单的身高和体重计算的 测量。然而，BSA不能解释瘦体重(LBM)和脂肪组织的差异 (At)。身高和体重相同的个体LBM和AT的分布可能有显著差异， 这可能会导致药物分布、清除量和药物相关毒性的变化。来自多个国家的数据 基于人群的大型研究表明，在体重指数相似的女性中，平均而言， 与非西班牙裔黑人相比，西班牙裔黑人骨骼肌比例更高，AT比例更低 西班牙裔白人。这些身体成分的差异可能意味着使用标准化疗 剂量(通过临床试验确定，参与者通常以白人为主)可能会导致许多 接受每公斤LBM次优化疗剂量的黑人妇女，增加了失败的风险 缓解、疾病进展或复发。然而，仍有一些关键问题需要澄清 在基于身体成分的药物剂量变化可以在临床试验中评估之前，包括 身体成分指标与最佳治疗结果相关，以及服药是否应该集中在 仅在LBM上，或也包括肥胖测量。为了解决我们改善乳腺癌的长期目标 黑人妇女的总体治疗结果和消除结果差异，这项回顾性研究 400名接受乳腺癌治疗的女性(大约44%的白人和45%的黑人)将使用现有的 计算机断层扫描测量身体成分并实现以下特定目标：1) 确定接受安慰剂治疗的白人和黑人女性之间的药物剂量/公斤体重的差异程度 以蒽环类或紫杉烷为主的化疗方案治疗浸润性乳腺癌，2)确定范围 药物剂量/公斤LBM和腹部AT的测量独立地和联合地与 化疗毒性和完成预定治疗。拟议中的研究结果将有助于 关于乳腺癌女性身体成分的重要基础数据，以及身体如何 组成可能会因种族而异。如果身体成分测量被发现与化疗有关- 相关毒性，药物剂量可以根据个人的身体成分量身定做，以便最大限度地 治疗效果，同时最大限度地减少与治疗相关的毒性。

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.