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

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.

项目总结/文摘