Breast White Adipose Tissue Inflammation and Breast Cancer Outcomes

乳房白色脂肪组织炎症和乳腺癌结果

基本信息

批准号：
10627750
负责人：
Neil Mukund Iyengar
金额：
$ 92.06万
依托单位：
KAISER FOUNDATION RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10627750
关键词：
Adipocytes Adipose tissue Affect Alcohol consumption Anabolism Aromatase Biological Assay Biological Markers Blood specimen Body Composition Body Size Body mass index Breast Breast Cancer Prognostic Factor Breast Cancer Risk Factor Breast Cancer Treatment California Cancer Prognosis Cessation of life Characteristics Clinical Crowns Data Development Diagnosis Diagnostic Diet Dietary Practices Disease Disease Management Drug or chemical Tissue Distribution Dyslipidemias Electronic Health Record Enrollment Enzymes Estrogens Ethnic Origin Etiology Exhibits Female Formalin Funding Grant Hormone Receptor Image Incidence Inflammation Inflammatory Infrastructure Insulin Resistance Investigation Learning Macrophage Malignant Neoplasms Mammary Gland Parenchyma Mastectomy Measures Mediating Metabolic Metabolic Marker Metabolic dysfunction Metabolic syndrome Metabolism Obesity Outcome Paraffin Embedding Participant Pathway interactions Patient-Focused Outcomes Patients Physical activity Plasma Population Heterogeneity Postmenopause Prevalence Prognostic Factor Prospective, cohort study Race Recurrence Recurrent Malignant Neoplasm Reporting Resources Risk Factors Sampling Scanning Second Primary Cancers Severities Slide Smoking History Smoking Status Specimen Structure Surgical Pathology Time Tissue Embedding Tissues Visceral Weight Woman Work X-Ray Computed Tomography abdominal CT biobank breast cancer diagnosis breast cancer progression cancer diagnosis cancer epidemiology cancer recurrence cancer surgery cancer survival carcinogenesis clinical care cohort cytokine density estrogenic ethnic diversity high risk improved inflammatory marker innovation insight lifestyle factors malignant breast neoplasm member metabolic profile modifiable risk mortality novel novel marker racial diversity subcutaneous systemic inflammatory response

项目摘要

ABSTRACT Obesity and excess adiposity at the time of breast cancer diagnosis are associated with increased likelihood of recurrence and cancer-related death. Understanding the mechanisms by which excess adiposity affects breast cancer progression would provide critical insights into strategies to improve patient outcomes. We have identified a novel tissue-based inflammatory biomarker in breast adipose tissue, crown-like structures of the breast (CLS-B), that we have shown to be associated with obesity and dysregulated metabolic factors. The presence of CLS-B, which are comprised of an adipocyte surrounded by a “crown” of macrophages, indicates a state of inflammation in the breast white adipose tissue (B-WATi). We previously reported that B- WATi is associated with metabolic syndrome characteristics. Importantly, B-WATi is associated with increased breast cancer risk and shortened time to recurrence in women with metastatic disease. The Pathways Study, a prospective cohort study of women with invasive breast cancer supported by an NCI cancer epidemiology cohort infrastructure grant, provides an outstanding opportunity to conduct a large- scale, definitive investigation of the pathophysiologic state associated with B-WATi, and to investigate the association of B-WATi with breast cancer outcomes. From January 2006 to May 2013, we enrolled a racially- and ethnically-diverse cohort of 4,505 women soon after a breast cancer diagnosis in Kaiser Permanente Northern California (KPNC). Pathways Study participants provided blood specimens and reported on lifestyle factors, including diet and physical activity. Linkage to KPNC electronic health records captures details of cancer diagnosis and clinical care, and a biorepository of diagnostic slides and formalin-fixed, paraffin- embedded tissue blocks has been created from definitive breast cancer surgeries for all cohort members. We propose to determine B-WATi presence and severity in Pathways Study participants who underwent mastectomy (n=1,982), leveraging the substantial non-tumor breast tissue available in the biorepository. We also propose to assay systemic measures of inflammation and metabolic aberration, and examine measures of adipose tissue distribution in a subset of women with computed tomography (CT) images. Specific Aims are to: 1) Characterize the pathophysiological state of B-WATi in women with invasive breast cancer, including associations with lifestyle factors, adipose tissue distribution, and circulating cytokine and metabolic profiles; 2) Determine the associations between B-WATi and breast cancer outcomes; and, 3) Examine whether the associations between B-WATi and breast cancer outcomes vary by lifestyle factors and other breast cancer prognostic factors such as race/ethnicity, hormone receptor status, stage of disease, and breast cancer treatment. This project brings together ground-breaking and innovative work on B-WATi with the outstanding resources and infrastructure of the Pathways Study. It promises to provide insight into the impact of B-WATi on breast cancer and to identify actionable and modifiable risk factors to improve breast cancer outcomes.

抽象的乳腺癌诊断时的肥胖和过度肥胖与乳腺癌的增加有关复发和癌症相关死亡的可能性。了解过度肥胖的机制。影响乳腺癌进展将为改善患者预后的策略提供重要见解。我们在乳房脂肪组织、冠状结构中发现了一种新型的基于组织的炎症生物标志物乳房（CLS-B），我们已经证明它与肥胖和代谢失调因素有关。 CLS-B 的存在，由被巨噬细胞“王冠”包围的脂肪细胞组成，表明乳房白色脂肪组织（B-WATi）处于炎症状态，我们之前报道过 B-。 WATi 与代谢综合征特征相关，重要的是，B-WATi 与增加相关。患有转移性疾病的女性患乳腺癌的风险和复发时间缩短。 Pathways 研究是一项针对患有浸润性乳腺癌的女性的前瞻性队列研究，由 NCI 癌症流行病学队列基础设施拨款，提供了一个绝佳的机会来开展大规模的量表，对与 B-WATi 相关的病理生理状态进行明确的研究，并研究从 2006 年 1 月到 2013 年 5 月，我们招募了一个种族- WATi 与乳腺癌结果的关联。以及凯撒医疗机构 (Kaiser Permanente) 诊断出乳腺癌后不久的 4,505 名不同种族女性队列北加州 (KPNC) 途径研究参与者提供了血液样本并报告了生活方式。因素，包括饮食和身体活动，与 KPNC 电子健康记录的链接可捕获详细信息。癌症诊断和临床护理，以及诊断载玻片和福尔马林固定、石蜡的生物储存库嵌入式组织块是通过明确的乳腺癌手术为所有队列成员创建的。我们建议确定接受过 B-WATi 治疗的 Pathways 研究参与者中是否存在 B-WATi 及其严重程度乳房切除术（n=1,982），利用生物储存库中可用的大量非肿瘤乳腺组织。还提出了炎症和代谢异常的系统性测定方法，并检查了通过计算机断层扫描 (CT) 图像了解一部分女性的脂肪组织分布。目的： 1) 描述患有浸润性乳腺癌的女性中 B-WATi 的病理生理状态，包括与生活方式因素、脂肪组织分布以及循环细胞因子和代谢特征的关联2) 确定 B-WATi 与乳腺癌结果之间的关联；3) 检查是否 B-WATi 与乳腺癌结果之间的关联因生活方式因素和其他乳腺癌而异预后因素，例如种族/民族、激素受体状态、疾病阶段和乳腺癌该项目将 B-WATi 的突破性创新工作与杰出的技术结合在一起。路径研究的资源和基础设施它有望提供对 B-WATi 影响的深入了解。乳腺癌并确定可操作和可改变的风险因素以改善乳腺癌的结果。