Mechanisms of racial disparity in breast cancer-related lymphedema

乳腺癌相关淋巴水肿的种族差异机制

基本信息

批准号：
10606708
负责人：
Andrea Barrio
金额：
$ 73.46万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606708
关键词：
Adjuvant Chemotherapy Age Anti-Inflammatory Agents Asian Atopic Dermatitis Automobile Driving Axillary Lymph Node Dissection Biology Biopsy Biopsy Specimen Black Populations Black race Body mass index Breast Cancer Risk Factor Breast Cancer Treatment Cardiovascular Diseases Caring Caucasians Cells Characteristics Chronic Clinical Complication Confounding Factors (Epidemiology)Deposition Developed Countries Development Disease Eligibility Determination Epidermis Epithelium Exposure to Fibroblasts Fibrosis Functional disorder Harvest High Prevalence Hospitalization Immune response Inflammation Inflammatory Inflammatory Response Injury Institutional Review Boards Keloid Knowledge Lead Link Liquid substance Lymph Lymphatic Lymphatic function Lymphedema Measurement Measures Mesenchymal Multivariate Analysis Neoadjuvant Therapy Operative Surgical Procedures Pathologic Patients Play Procedures Publishing Qualifying Quality of life Race Reporting Research Risk Risk Factors Role Sampling Sentinel Lymph Node Biopsy Serum Skin Specimen Swelling Testing Time Tissues Treatment Efficacy Woman antifibrotic treatment arm black men black patient black women cohort efficacy testing high risk inflammatory modulation keratinocyte lymph nodes lymphatic dysfunction malignant breast neoplasm melanoma novel therapeutics patient population prevent prophylactic prospective racial difference racial disparity radiation response recurrent infection response skin disorder skin fibrosis

项目摘要

PROJECT SUMMARY/ABSTRACT This proposal is significant because we aim to study the cellular mechanisms that regulate the increased risk of breast cancer-related lymphedema (BCRL) development in Black women. This is important because BCRL is a highly morbid disease that causes chronic and progressive arm swelling. Patients who develop BRCL have diminished quality of life, require life-long care with compression garments, and can develop recurrent infections that require hospitalization. Due to the high prevalence of breast cancer, BCRL is the most common form of lymphedema in developed countries, afflicting 20–35% of women who undergo axillary lymph node dissection (ALND). To identify risk factors for BCRL, our group has prospectively followed 276 women with arm measurements before and after ALND for 2 years. We have found that Black women have the highest risk of BCRL even after adjusting for confounding variables. In our study, Black race increased the risk of BCRL development by >3.6 fold compared with White race. These findings are supported by two other published studies reporting increased risk of BCRL development in Black women who undergo ALND for breast cancer. Thus, while there is strong evidence that Black women have a significantly increased risk of developing BCRL, the cellular mechanisms that regulate this risk remain unknown. This gap in our knowledge is important and a major barrier to developing novel therapies that prevent or treat lymphedema in this patient population. In addition, understanding how Black race increases the risk of BCRL may shed light on the mechanisms that regulate the pathophysiology of this disease in general. Based on prior research and our preliminary studies, our central hypothesis is that Black women have an increased risk of developing BCRL due to a baseline increased propensity for inflammation and fibrosis. We propose to test this hypothesis using two Specific Aims. In Aim 1, we will analyze how racial disparities modulate inflammatory responses following lymphatic injury. This hypothesis is based on the finding that the pathophysiology of lymphedema is linked to chronic inflammation and development of T-helper 2 (Th2)-biased immune responses. Black patients have a propensity for inflammation in other pathological settings, suggesting that these differences may also contribute to an increased risk for developing BCRL. In Aim 2, we will test the hypothesis that Black women have an increased fibrotic response to lymphedema. This hypothesis is based on the observation that fibrosis is a key pathological feature of lymphedema and plays a major role in regulating lymphatic function. Black individuals have an increased potential for fibrosis in a variety of pathological settings including inflammatory skin disorders.

项目概要/摘要这个提议很重要，因为我们的目标是研究调节细胞的机制黑人女性患乳腺癌相关淋巴水肿 (BCRL) 的风险增加，这一点很重要。因为 BCRL 是一种高发病率的疾病，会导致患者出现慢性进行性手臂肿胀。患有 BRCL 的人生活质量下降，需要使用压缩衣进行终身护理，并且可能由于乳腺癌的高患病率，BCRL 会出现需要住院治疗的反复感染。发达国家最常见的淋巴水肿形式，20-35% 的接受过淋巴水肿治疗的女性患有该病腋窝淋巴结清扫术（ALND）。为了确定 BCRL 的危险因素，我们的小组前瞻性地跟踪了 276 名患有手臂疾病的女性。我们对 ALND 前后两年的测量结果发现，黑人女性患此病的风险最高。即使在调整混杂变量后，BCRL 仍会增加。与白人相比，发育超过 3.6 倍这些发现得到了另外两项已发表的研究结果的支持。研究报告称，接受 ALND 治疗乳腺癌的黑人女性发生 BCRL 的风险增加。因此，虽然有强有力的证据表明黑人女性患 BCRL 的风险显着增加，调节这种风险的细胞机制仍然未知。我们的知识差距很重要，而且是一个重要的问题。开发预防或治疗该患者群体淋巴水肿的新疗法的主要障碍。此外，了解黑人种族如何增加 BCRL 的风险可能会揭示以下机制：根据先前的研究和我们的初步研究，总体上调节这种疾病的病理生理学。我们的中心假设是，由于基线，黑人女性患 BCRL 的风险增加我们建议使用两个具体目标来检验这一假设。在目标 1 中，我们将分析种族差异如何调节淋巴损伤后的炎症反应。该假说基于以下发现：淋巴水肿的病理生理学与慢性淋巴水肿有关。黑人患者的炎症和 T 辅助细胞 2 (Th2) 偏向性免疫反应的发展。其他病理环境中炎症的倾向，表明这些差异也可能导致罹患 BCRL 的风险增加在目标 2 中，我们将检验黑人女性的假设。对淋巴水肿的纤维化反应增加。该假设基于纤维化的观察。是淋巴水肿的一个关键病理特征，在调节淋巴功能中起重要作用。个体在各种病理情况下（包括炎症）发生纤维化的可能性增加皮肤疾病。