Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.
Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.
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DOI：
10.1158/1078-0432.ccr-15-2239
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发表时间：
2016-05-01
期刊：
影响因子：
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通讯作者：
Dannenberg AJ
中科院分区：
文献类型：
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作者：
Iyengar NM;Zhou XK;Gucalp A;Morris PG;Howe LR;Giri DD;Morrow M;Wang H;Pollak M;Jones LW;Hudis CA;Dannenberg AJ
肥胖、胰岛素抵抗和循环促炎介质水平升高与早期乳腺癌预后较差有关。为了研究白色脂肪组织(WAT)炎症是否代表一种潜在的统一机制，我们研究了乳房WAT炎症与代谢综合征的关系及其预后重要性。WAT炎症的定义是存在死亡/死亡的脂肪细胞，周围有形成乳房冠状结构的巨噬细胞(CLS-B)。在横断面研究(队列1)和回溯性研究(队列2)中对两个独立的组进行了检查。队列1包括为降低乳腺癌风险(n=10)或治疗乳腺癌(n=90)而接受乳房切除术的100名妇女。以CLS-B状态比较代谢综合征相关循环因子。CLS-B和代谢综合征的相关性在队列2中得到了验证，该队列包括127名患转移性乳腺癌的女性。按CLS-B评分比较无复发远期生存率(DRFS)。在队列1和队列2中，分别有52/100(52%)和52/127(41%)患者检测到乳房水炎。在队列1中，乳房水炎患者的胰岛素、血糖、瘦素、甘油三酯、C反应蛋白和白介素6升高，而高密度脂蛋白和脂联素降低(P<；0.05)。在队列2中，乳房水炎与高脂血症、高血压和糖尿病相关(P<；0.05)。与无乳房水炎症的患者相比，有炎症的患者发生dRFS的调整风险比为1.83(95%可信区间为1.07~3.13)。WAT炎症是一种临床上难以捉摸的过程，有助于解释代谢综合征与乳腺癌预后不良之间的关系。
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 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. 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. WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis.