Abstract Title:

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

Abstract Source:

Clin Cancer Res. 2015 Dec 28. Epub 2015 Dec 28. PMID: 26712688

Abstract Author(s):

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

Article Affiliation:

Neil M Iyengar

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 of the breast (CLS-B). 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-B 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 52/100 (52%) and 52/127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and interleukin-6; and lower HDL 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 to patients without breast WAT inflammation, the adjusted hazard ratio for dRFS was 1.83 (95% CI, 1.07 to 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.

Study Type : Human Study

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