title: Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.
abstract: Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.
  
  
  
  WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.
  
  
  
  In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07-3.13) for patients with inflammation.
  
  
  
  WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283-9. ©2015 AACR.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Iyengar
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Xi Kathy
authors.initials: XK
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ayca
authors.initials: A
authors.lastname: Gucalp
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.affiliation: Department of Cell & Developmental Biology, Weill Cornell Medical College, New York, New York.
authors.forename: Louise R
authors.initials: LR
authors.lastname: Howe
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Dilip D
authors.initials: DD
authors.lastname: Giri
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Departments of Medicine and Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York. ajdannen@med.cornell.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dannenberg
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D014280:Triglycerides / Q000378:metabolism
chemical_list: D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D014280:Triglycerides; D002097:C-Reactive Protein; D005947:Glucose