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

• 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
• 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; 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

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.

项目摘要/摘要 该提议很重要，因为我们旨在研究调节调节的细胞机制 黑人妇女中与乳腺癌相关的淋巴水肿（BCRL）发育的风险增加。这很重要 因为BCRL是一种高度病态的疾病，会导致慢性和进行性臂肿胀。患者 发展BRCL的生活质量降低，需要压缩服装终身护理，并且可以 发展需要住院的复发感染。由于乳腺癌的患病率很高，BCRL为 发达国家最常见的淋巴水肿形式，遭受了20-35％的妇女 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关注了276名妇女 ALND之前和之后的测量2年。我们发现黑人妇女的风险最高 即使调整了混杂变量后，BCRL也是如此。在我们的研究中，黑人种族增加了BCRL的风险 与白色种族相比，开发> 3.6倍。这些发现得到了另外两个已发表的支持 研究报告的研究增加了患有乳腺癌ALND的黑人妇女的BCRL发展风险。 尽管有充分的证据表明黑人妇女患BCRL的风险显着增加，但 调节这种风险的细胞机制仍然未知。我们知识上的这一差距很重要，一个 在该患者人群中开发预防或治疗淋巴水肿的新型疗法的主要障碍。在 此外，了解黑人种族如何增加BCRL的风险可能会阐明 总体上调节该疾病的病理生理学。根据先前的研究和我们的初步研究 我们的中心假设是，由于基线，黑人妇女患BCRL的风险增加了 感染和纤维化的倾向增加。我们建议使用两个特定目标检验这一假设。 在AIM 1中，我们将分析种族分布如何调节淋巴损伤后的炎症反应。 该假设基于以下发现：淋巴水肿的病理生理学与慢性有关 T-助手2（TH2）偏置的免疫反应的炎症和发育。黑人患者有 在其他病理环境中炎症的倾向，表明这些差异也可能 有助于增加BCRL的风险。在AIM 2中，我们将测试黑人妇女的假设 对淋巴水肿的纤维化反应增加。该假设是基于纤维化的观察结果 是淋巴水肿的关键病理特征，在控制淋巴功能中起着重要作用。黑色的 在包括炎症的各种病理环境中，个体具有纤维化的潜力增加 皮肤疾病。