Prognostic and predictive value of thymidine phosphorylase activity in early-stage breast cancer patients

Clin Breast Cancer. 2002 Apr;3(1):55-64. doi: 10.3816/cbc.2002.n.012.


The antitumor effects of 5-fluorouracil (5-FU) and its derivatives depend upon the activity of nucleoside metabolic enzymes in tumor tissues. Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine, to 5-FU. The relationship between TP expression in tumor tissues and patient survival was retrospectively examined in early-stage breast cancer patients treated with either oral 5'-DFUR administered for 6 months or surgery alone in a prospective randomized controlled trial. Thymidine phosphorylase expression in tumor cells and tumor-associated stromal (TAS) cells was examined by immunohistochemistry in 650 tissue samples from patients in this trial (n = 1217). Eight-year follow-up data showed that high TP expression in tumor cells was a significant prognostic indicator of a favorable outcome only for the patients in the 5'-DFUR group. Thus, TP expression was shown to be a predictive factor of 5'-DFUR efficacy. Conversely, a low TP expression in TAS cells was also a potent favorable prognostic indicator. These results on TP status in 2 tumor cell types could provide novel information for predicting prognosis for a patient subgroup, which would receive a probable therapeutic effect from 5'-DFUR, and presumably, from adjuvant therapy of capecitabine in early-stage breast cancer. Determination of TP status might also identify a patient subgroup whose prognosis is quite favorable even without adjuvant therapy. Further investigations on prognostic and predictive implications of TP activity in a clinical setting are warranted.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Floxuridine / administration & dosage
  • Floxuridine / therapeutic use
  • Humans
  • Japan
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Stromal Cells / metabolism
  • Survival Analysis
  • Thymidine Phosphorylase / metabolism*
  • Tumor Cells, Cultured / metabolism


  • Antimetabolites, Antineoplastic
  • Floxuridine
  • Thymidine Phosphorylase
  • doxifluridine