Thymidylate synthase and thymidine phosphorylase as predictive markers of capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer

Purpose: 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). Methods: 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/m²/day) for 14 days every 3 weeks. Results: 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). Conclusions: 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.