Abstract P6-13-04: Thymidylate Synthase (TS) and Thymidine Phosphorylase (TP) Expression as Predictive Markers of Capecitabine Mono-Chemotherapy for Patients with Anthracyclin-Taxane Pretreated Metastatic Breast Cancer (MBC)

Abstract

Abstract Background: Capecitabine, one of the widely used cytotoxic agents for breast cancer, achieved high tumor control rate with low toxicity even in heavily-pretreated patients with metastatic breast cancer (MBC). Capecitabine (Xeloda®) is an oral fluoropyrimidine pro-drug that is transformed to fluorouracil (FU) in several steps, the last of which is conversion of 5'-deoxy-5-fluorouridine to FU by TP. And TS is a target enzyme of 5-FU. The primary purpose of this study was to evaluate the role of TS and TP as biomarkers to predict clinical outcomes of capecitabine monotherapy for MBC. Method: Of Three hundreds fifty-three patients with MBC treated with capecitabine at Samsung Medical Center from 2000 to 2008, ninety patients who were previously treated with anthracycline and taxanes containing regimens and had available tissues for immunohistochemical stainings with estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor-2 (HER2), TS, and TP were included in this analysis. All patients had received capecitabine 2000-2500mg/m2/day for 14days q 3 weeks. Results: The median age of these 90 patients was 49 (26-76) years. The response rate (RR) was 25.6% and the disease control rate (DCR) was 65.6%. The median progression-free survival (PFS) and overall survival (OS) from the 1st day of capecitabine monotherapy were 4.8 (95% C.I.; 3.1-6.5) and 26.7 (95% C.I.; 17.1-36.3) months, respectively. High TS expression (TS score ≥100) was more common in patients with triple negative (TN) subtype than in those with other subtypes (16% for HR+, 22% for HER2+, 44% for TN, p=0.023). Median PFS was significantly lower in high TS expression (6.6 vs. 3.0 months; p=0.017) and low TP expression (TP<50) patients (6.0 vs. 3.3 months; p=0.013). High TS score and low TP score were identified as unfavorable independent risk factors for PFS to capecitabine monotherapy in Cox regression multivariate analysis (Hazard Ratio (HR) 1.7, p=0.037 for high TS score; HR 1.8, p=0.014 for low TP score). And, high TS and low TP score were associated with poorer overall survival.(29.9 vs. 14.1 months; p=0.008 for TS /29.9 vs. 20.4 months; p=0.043 for TP) Conclusion: Our data suggests that high TS score and low TP score correlated with shorter PFS for capecitabine monotherapy of patients with anthracycline and taxane pretreated MBC. Potential role of TS, TP expression as predictive markers of capecitabine monotherapy in patient with MBC should be confirmed by prospective studies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-13-04.