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: 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
• 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

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.

摘要