TY - JOUR
T1 - Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer
AU - Iyengar, Neil M.
AU - Zhou, Xi Kathy
AU - Gucalp, Ayca
AU - Morris, Patrick G.
AU - Howe, Louise R.
AU - Giri, Dilip D.
AU - Morrow, Monica
AU - Wang, Hanhan
AU - Pollak, Michael
AU - Jones, Lee W.
AU - Hudis, Clifford A.
AU - Dannenberg, Andrew J.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-15-2239
DO - 10.1158/1078-0432.CCR-15-2239
M3 - Article
C2 - 26712688
AN - SCOPUS:84968739477
VL - 22
SP - 2283
EP - 2289
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -