Impact of Allostatic Load and Neighborhood Contextual Factors on Breast Cancer in the Women's Health Initiative

项目摘要/摘要 非西班牙裔黑人(NHB)和西班牙裔/拉丁裔女性被诊断为乳房的比例不成比例 肿瘤表现出更具侵袭性的表型；NHB妇女死于乳腺癌的比率 比美国其他所有种族/民族都要高。由于结构性种族主义(及其 下游效应)，NHB和西班牙裔/拉丁裔女性相比经历了更多的慢性压力源 给非西班牙裔白人(NHW)女性。来自我们团队和其他人的新兴数据显示，社交和 生物因素导致肿瘤特征更具侵袭性的乳腺癌的发展 这会导致更糟糕的结果。有证据支持平衡负荷--这是一种衡量 主要生理系统，包括新陈代谢、心血管和免疫/炎症系统- 作为衡量累积生理压力和不利健康后果的风险因素的一种手段。数据来自 一项具有全国代表性的美国女性样本显示，不平衡负荷与 与黑人女性的社会经济地位(SES)和乳腺癌呈正相关， 但不是白人女性。先前没有研究前瞻性地探讨过静负荷和 在一个大的、多样化的研究样本中，邻里环境因素(同时)对乳腺癌有影响。 在这里，我们建议检查诊断前的稳态负荷评分(ALS)的影响，并客观地 测量的周边环境因素对乳腺癌发病率和表型的影响， 妇女健康中NHB、NHW和西班牙裔/拉丁裔参与者的嵌套病例对照研究 主动性(WHI)。我们的中心假设是乳腺癌和侵袭性肿瘤的风险 可归因于较高的肌萎缩侧索硬化症以及社会经济贫困和种族隔离的影响 邻里关系。此外，我们还假设，恒定负荷调节了 与乳腺癌有关的社区背景，这因种族/民族而异。利用WHI的前景 设计，丰富的流行病学和临床数据，以及长期的随访，通过 目的如下：1)研究不平衡负荷与乳腺癌风险和肿瘤的关系 表型；2)调查邻里环境因素与乳腺癌风险和 肿瘤表型；以及3)评估异位负荷和肿瘤表型之间的独立关联 患乳腺癌的社区背景因种族/民族而异。这项研究将在以下方面产生重大影响 产生了关于不利的邻里环境因素和 非平衡负荷(作为邻域环境和环境之间的中间生物过程/机制 健康)对乳腺癌的影响。这项研究的发现将有助于对生物的新知识 结构性种族主义的长期影响的基础和肌萎缩侧索硬化症作为癌症风险生物标记物的实用性。这些 数据对于制定以证据为基础的预防战略以改善癌症健康公平至关重要。

PROJECT SUMMARY/ABSTRACT Non-Hispanic Black (NHB) and Hispanic/Latinx women are disproportionately diagnosed with breast tumor exhibiting more aggressive phenotypes; and NHB women are dying from breast cancer at rates higher than every other racial/ethnic group in the United States (US). Due to structural racism (and its downstream effects), NHB and Hispanic/Latinx women experience more chronic stressors compared to non-Hispanic White (NHW) women. Emerging data, from our group and others, show that social and biologic factors contribute to the development of breast cancers with more aggressive tumor features that lead to the poorer outcomes. Evidence supports allostatic load – a measure of dysregulation across major physiologic systems including metabolic, cardiovascular, and immune/inflammatory systems – as a measure of cumulative physiologic stress and risk factor for adverse health outcomes. Data from a nationally representative sample of US women showed that allostatic load is inversely associated with socioeconomic status (SES) and positively associated with breast cancer among Black women, but not White women. No prior study has prospectively explored the impact of allostatic load and neighborhood contextual factors (simultaneously) on breast cancer in a large, diverse study sample. Here we propose to examine the impact of pre-diagnostic allostatic load score (ALS) and objectively measured neighborhood contextual factors on breast cancer incidence and phenotype in a large, nested case-control study of NHB, NHW, and Hispanic/Latinx participants in the Women’s Health Initiative (WHI). Our central hypothesis is that risk of breast cancer and aggressive tumors are attributable to the impact of higher ALS and socioeconomically deprived and racially segregated neighborhood context. Further, we hypothesize that allostatic load mediates the associations of neighborhood context with breast cancer, which differ by race/ethnicity. Leveraging WHI’s prospective design, rich epidemiologic and clinical data, and long-term follow-up, to test these hypotheses through the following aims: 1) Investigate associations of allostatic load with breast cancer risk and tumor phenotype; 2) Investigate associations of neighborhood contextual factors with breast cancer risk and tumor phenotype; and 3) Evaluate whether independent associations of allostatic load and neighborhood context with breast cancer differ by race/ethnicity. This study will have a high impact by yielding novel, prospective data on the impact of unfavorable neighborhood contextual factors and allostatic load (as an intermediate biological process/mechanism between neighborhood context and health) on breast cancer. Findings from this study will contribute new knowledge about the biological basis of long-term effects of structural racism and utility of ALS as a biomarker of cancer risk. These data are essential to developing evidence-based prevention strategies to improve cancer health equity.