CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence
CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence
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DOI：
10.1634/theoncologist.2009-0161
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发表时间：
2009-01-01
期刊：
影响因子：
5.8
通讯作者：
Cristofanilli, Massimo
中科院分区：
文献类型：
--
作者：
Andre, Fabrice;Xia, Weiya;Cristofanilli, Massimo
背景趋化因子受体4（CXCR 4）已被证明在早期转移过程中具有关键作用。本研究的目的是评估CXCR 4表达在原发性乳腺肿瘤中的预后价值，并描述与表达CXCR 4配体基质细胞衍生因子1的器官中转移发生的相关性（即，肝、肺、脑和骨）。通过免疫组织化学方法对两项前瞻性临床试验中的823例原发性乳腺肿瘤患者的CXCR 4表达进行了评估。当>1%的肿瘤细胞被染色时，CXCR 4表达被认为是阳性的。CXCR 4表达的预后价值通过校正临床特征的考克斯回归模型进行评估。我们评估了CXCR 4表达与特定器官远处转移率的关系。CXCR 4在794例原发性肿瘤中的92例（12%）中表达。CXCR 4表达与临床特征无关。CXCR 4对总生存率无预后意义，且显示出无显著性的远处转移风险增高趋势。CXCR 4（+）肿瘤显示骨转移的风险显著较高。CXCR 4（+）和CXCR 4（-）肿瘤的10年骨转移发生率分别为23%（13.6%~ 32.6%）和12%（9.7%~ 15%）。这项研究表明，CXCR 4在原发性乳腺肿瘤中的表达与发生骨转移的可能性较高相关。这一发现可能为开发新的佐剂策略开辟新的途径，包括骨靶向药物。肿瘤学家2009; 14：1182-1188
Background. Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to evaluate the prognostic value of CXCR4 expression in primary breast tumors and describe correlations with the occurrence of metastasis in organs expressing the CXCR4 ligand stromal cell-derived factor 1 (i.e., liver, lung, brain, and bone).Patients and Methods. CXCR4 expression in primary breast tumors was evaluated by immunohistochemistry in 823 patients included in two prospective clinical trials. CXCR4 expression was considered positive when >1% of tumor cells were stained. The prognostic value of CXCR4 expression was assessed by a Cox regression model adjusted for clinical characteristics. We assessed the association of CXCR4 expression with the rate of distant metastasis to specific organ sites.Results. CXCR4 was expressed in 92 of 794 primary tumors (12%). CXCR4 expression was not associated with clinical characteristics. CXCR4 was not prognostic for overall survival and showed a nonsignificant trend toward a higher risk for distant metastasis. CXCR4(+) tumors showed a significantly higher risk for bone metastasis. The 10-year incidences of bone metastases were 23% (13.6%-32.6%) and 12% (9.7%-15%) in CXCR4(+) and CXCR4(-) tumors, respectively.Conclusion. This study suggests that expression of CXCR4 in primary breast tumors is associated with a higher likelihood of developing bone metastases. This finding could open new avenues for the development of novel adjuvant strategies, including bone-targeting agents. The Oncologist 2009; 14: 1182-1188