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

• 批准号: 10397584
• 负责人: Neil Mukund Iyengar
• 金额: $ 92.66万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 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/10397584
• 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; Data; Dental crowns; 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; Lead; 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; 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; base; 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; macrophage; malignant breast neoplasm; member; metabolic profile; modifiable risk; mortality; novel; novel marker; racial diversity; subcutaneous; systemic inflammatory response

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 乳腺癌诊断时肥胖和超过肥胖与增加有关 复发和与癌症相关的死亡的可能性。了解超过肥胖的机制 影响乳腺癌的进展将为改善患者预后的策略提供关键的见解。 我们已经确定了一种新型的基于组织的炎症生物标志物在乳腺脂肪组织，冠状结构 乳房（CLS-B）的表明，我们已证明与肥胖症和代谢因子失调有关。 Cls-B的存在由巨噬细胞的“冠”围绕着脂肪细胞组成， 表示乳腺白脂肪组织（B-WATI）的炎症状态。我们以前报道了b- WATI与代谢综合征特征有关。重要的是，b-wati与增加有关 乳腺癌的风险和转移性疾病女性复发时间缩短。 途径研究，一项针对侵入性乳腺癌女性的前瞻性队列研究 NCI癌症流行病学队列基础设施赠款提供了一个出色的机会，以进行大型 比例，与B-WATI相关的病理生理状态的确切投资，并调查 B-WATI与乳腺癌结局的关联。从2006年1月到2013年5月，我们参加了种族活动 - 在Kaiser Permanente进行乳腺癌诊断后不久，有4,505名妇女的种族多样性队列 北加州（KPNC）。途径研究参与者提供了血液标本并报告了生活方式 因素，包括饮食和体育锻炼。与KPNC电子健康记录的联系捕获了 癌症诊断和临床护理，以及诊断幻灯片和福尔马林固定的石蜡的生物座 已为所有队列成员的确定乳腺癌手术创建了嵌入式组织块。 我们建议在研究参与者的途径中确定B-WATI的存在和严重性 乳房切除术（n = 1,982），利用生物疗法中可用的大量非肿瘤乳腺组织。我们 还提出了主张系统性炎症和代谢畸变的措施，并检查 具有计算机断层扫描（CT）图像的女性子集中的脂肪组织分布。具体目标是 TO：1）表征侵入性乳腺癌女性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谱的关联； 2） 确定B-WATI与乳腺癌结局之间的关联； 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 诸如种族/种族，骑马受体状况，疾病和乳腺癌等预后因素 治疗。该项目汇集了B-WATI的开创性和创新作品以及杰出的 途径研究的资源和基础设施。它有望洞悉B-WATI的影响 关于乳腺癌并确定可起诉和可修改的危险因素以改善乳腺癌的结局。