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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.

SUBMITTER: Iyengar NM 

PROVIDER: S-EPMC4854755 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Iyengar Neil M NM   Zhou Xi Kathy XK   Gucalp Ayca A   Morris Patrick G PG   Howe Louise R LR   Giri Dilip D DD   Morrow Monica M   Wang Hanhan H   Pollak Michael M   Jones Lee W LW   Hudis Clifford A CA   Dannenberg Andrew J AJ  

Clinical cancer research : an official journal of the American Association for Cancer Research 20151228 9


<h4>Purpose</h4>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.<h4>Experimental design</h4>WAT inflammation was defined by the presence of dead/dying adipocytes surro  ...[more]

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