Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer

Neil M. Iyengar, Xi Kathy Zhou, Ayca Gucalp, Patrick G. Morris, Louise R. Howe, Dilip D. Giri, Monica Morrow, Hanhan Wang, Michael Pollak, Lee W. Jones, Clifford A. Hudis, Andrew J. Dannenberg

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis.

Original languageEnglish (US)
Pages (from-to)2283-2289
Number of pages7
JournalClinical Cancer Research
Volume22
Issue number9
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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