Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cancer Chemother Pharmacol. 2011 Sep;68(3):743-51. doi: 10.1007/s00280-010-1545-0. Epub 2010 Dec 18.
The primary purpose of this study was to evaluate the role of thymidylate synthase (TS) and thymidine phosphorylase (TP) as biomarkers to predict clinical outcomes of capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC).
Of the patients who were previously treated with anthracycline and taxane regimens, 90 patients who had available tissue block for immunohistochemistry with measurable lesions were included. All patients received capecitabine (2,500 mg/m(2)/day) for 14 days every 3 weeks.
High TS expression was more common among patients with triple-negative (TN) subtype than among patients with other subtypes (33% for hormone receptor+, 8% for HER2+, and 58% for TN, P = 0.023). The median PFS was significantly lower in patients with high TS (6.6 vs. 3.0 months; P = 0.017) and low TP expressions (6.0 vs. 3.3 months; P = 0.013). A high TS and a low TP expressions were identified as unfavorable independent risk factors for PFS to capecitabine monotherapy in multivariate analysis (hazard ratio [HR], 1.7, P = 0.037 for high TS score; HR, 1.8, P = 0.014 for low TP score).
Our data suggest that high TS and low TP scores correlate with a shorter PFS for capecitabine monotherapy in patients with anthracycline- and taxane-pretreated MBC.
本研究的主要目的是评估胸苷酸合成酶（TS）和胸苷磷酸化酶（TP）作为生物标志物预测蒽环类和紫杉烷类预处理转移性乳腺癌（MBC）患者接受卡培他滨单药治疗的临床结局的作用。
在先前接受蒽环类和紫杉烷类方案治疗的患者中，纳入了 90 名有可测量病变的组织块进行免疫组织化学检查的患者。所有患者均接受卡培他滨（2500mg/m2/天）治疗，每 14 天为一个周期，每 3 周给药一次。
三阴性（TN）亚型患者中高 TS 表达更为常见（激素受体阳性患者为 33%，HER2 阳性患者为 8%，TN 患者为 58%，P=0.023）。高 TS 表达（6.6 个月 vs. 3.0 个月；P=0.017）和低 TP 表达（6.0 个月 vs. 3.3 个月；P=0.013）患者的中位 PFS 显著降低。多变量分析显示，高 TS 和低 TP 表达被确定为卡培他滨单药治疗 PFS 的不利独立危险因素（高 TS 评分的危险比 [HR]，1.7，P=0.037；低 TP 评分的 HR，1.8，P=0.014）。
我们的数据表明，在蒽环类和紫杉烷类预处理的 MBC 患者中，高 TS 和低 TP 评分与卡培他滨单药治疗的较短 PFS 相关。
