Mechanisms of racial disparity in breast cancer-related lymphedema

项目摘要/摘要 这一建议意义重大，因为我们的目标是研究调节 黑人女性罹患乳腺癌相关淋巴水肿(BCRL)的风险增加。这事很重要 因为BCRL是一种高度病态的疾病，会导致慢性和进行性手臂肿胀。患者 患有BRCL降低了生活质量，需要终生护理和压缩服装，并且可以 出现需要住院治疗的反复感染。由于乳腺癌的高发病率，BCRL是 淋巴水肿是发达国家最常见的一种淋巴水肿，20%-35%的女性患有淋巴水肿 腋窝淋巴结清扫术(ALND)。 为了确定BCRL的危险因素，我们小组前瞻性地跟踪了276名患有ARM的女性 ALND前后2年的测量结果。我们发现，黑人女性患癌症的风险最高 即使在对混杂变量进行调整后，BCRL也是如此。在我们的研究中，黑人种族增加了BCRL的风险 与白人相比，&gt；的发展是3.6倍。这些发现得到了另外两篇已发表的论文的支持 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，尽管有强有力的证据表明，黑人女性患BCRL的风险显著增加， 调节这种风险的细胞机制仍不清楚。我们知识中的这一差距是重要的，而且是 在这类患者中开发预防或治疗淋巴水肿的新疗法的主要障碍。在……里面 此外，了解黑人种族如何增加BCRL的风险可能有助于阐明 从总体上调节这种疾病的病理生理学。根据之前的研究和我们的初步研究， 我们的中心假设是，由于基线的原因，黑人女性患BCRL的风险增加 发炎和纤维化的倾向增加。我们建议使用两个特定的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。 这一假说是基于淋巴水肿的病理生理学与慢性 T辅助细胞2(Th2)偏向免疫反应的炎症和发展。黑人患者有一种 在其他病理环境中的炎症倾向，表明这些差异也可能 增加了发展BCRL的风险。在目标2中，我们将测试黑人女性 对淋巴水肿有更强的纤维化反应。这一假说是基于观察到的纤维化 是淋巴水肿的一个重要病理特征，在调节淋巴功能方面起着重要作用。黑色 在包括炎症性疾病在内的各种病理环境中，个体患纤维化的可能性增加。 皮肤病。

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.