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

Anti-Cancer Drugs, 04/06/2012

Zhao HY et al. – The results provide evidence that the thymidine phosphorylase (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.

Methods

  • The authors 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).

Results

  • 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.

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