Hilborn Erik, Sivik Tove, Fornander Tommy, Stål Olle, Nordenskjöld Bo, Jansson Agneta
Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 581 85, Linköping, Sweden,
Breast Cancer Res Treat. 2014 May;145(1):73-82. doi: 10.1007/s10549-014-2933-7. Epub 2014 Apr 9.
To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P < 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.
为了进一步研究与预后以及他莫昔芬治疗结果预测的关系,我们调查了随机接受辅助他莫昔芬治疗或未接受内分泌治疗的乳腺癌患者肿瘤中CXCL10和CXCR3的表达水平。对912例随机接受他莫昔芬治疗或未接受内分泌治疗的乳腺癌患者的组织芯片进行免疫组织化学检测。发现CXCR3状态是预测远处复发以及降低乳腺癌特异性生存率的一种预后工具。在雌激素受体(ER)阳性肿瘤患者中,与CXCL10表达较弱的肿瘤患者相比,CXCL10水平高的肿瘤患者在无局部复发生存率方面他莫昔芬治疗效果更好[风险比(RR)0.46(95%可信区间0.25 - 0.85,P = 0.01)]。此外,与CXCR3水平较弱的组[RR 1.33(95%可信区间0.38 - 4.79,P = 0.65)]相比,CXCR3表达强的ER阳性肿瘤患者在乳腺癌特异性生存率方面他莫昔芬治疗效果更好[RR 0.34(95%可信区间0.19 - 0.62,P < 0.001)]。我们首次在此表明,CXCL10和CXCR3表达都是他莫昔芬治疗患者良好预后的预测指标。