Evaluations of biomarkers associated with sensitivity to 5-fluorouracil and taxanes for recurrent/advanced breast cancer patients treated with capecitabine-based first-line chemotherapy

Abstract

The aim of the present study was to investigate the gene expression of biomarkers associated with the sensitivity to fluoropyrimidine and taxanes in recurrent/advanced breast cancer patients treated with first-line capecitabine chemotherapy. We evaluated the clinicopathological/prognostic significance of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), class III β-tubulin (βIII-tubulin), and stathmin-1 or oncoprotein-18 (STMN1). Formalin-fixed, paraffin-embedded tumor specimens from 42 patients were used for analysis of TS, DPD, TP, βIII-tubulin, and STMN1 expression with a real-time reverse transcription-PCR technique. Patients were classified into the high-expression and low-expression groups according to the median value of the expression level of each biomarker. There was a significantly longer time to progression (TTP) in the high-TP group (P=0.018). The multivariate analysis revealed that the TP expression (hazard ratio for the low-TP group vs. the high-TP group, 2.873; 95% confidence interval, 1.143-7.223; P=0.025) is independent of prognostic factors for TTP. In the subgroup of patients treated with capecitabine plus taxanes as first-line chemotherapy, TTP was significantly longer in the low-βIII-tubulin group (P=0.047). The gene expression of TS, DPD, and STMN1 failed to have any significant impact on the outcome. These results provide further evidence that the TP expression may be a prognostic factor in breast cancer patients treated with capecitabine-based first-line chemotherapy, and βIII-tubulin can be used to predict the outcome of capecitabine in combination with taxanes as first-line chemotherapy. Therefore, these potential biomarkers should be further evaluated.