Intratumoral pyrimidine nucleoside phosphorylase (PyNPase) activity predicts a selective effect of adjuvant 5'-deoxy-5-fluorouridine (5'DFUR) on breast cancer

Breast Cancer. 2000 Jan;7(1):37-41. doi: 10.1007/BF02967186.

Abstract

Background: Pyrimidine nucleoside phosphorylase (PyNPase) is the enzyme that converts 5'-deoxy-5-fluorouracil (5'DFUR) to 5-fluorouracil (5FU). Its activity in cancer tissue may correlate with the selective antitumor activity of 5'DFUR in breast cancer.

Methods: Two hundred and sixteen T2 breast cancer patients were treated consecutively with surgery followed by 5'DFUR (600 mg/body/day) + tamoxifen (20 mg/body/day) for 2 years. PyNPase activity in breast cancer tissue, determined by high-performance liquid chromatography, ranged from 4.2-626.0 micrograms FU/mg protein/hr (mean +/- SD, 203.5 +/- 122.4), and the examined patients were divided into two groups: group A (high PyNPase group), cases with the PyNPase activity equal to or more than the mean value of 203.5 micrograms FU/mg protein/hr, and group B (low PyNPase group), cases with activity less than the mean value.

Results: Although there was no difference in relapse-free survival (RFS) between groups A and B, among node-positive patients (n = 83) those in group A tended to have a longer RFS. When divided into subgroups according to estrogen receptor (ER) status, among node-positive and ER-positive tumors (n = 49), the RFS was significantly better in group A than in group B (p < 0.05).

Conclusion: Intratumoral PyNPase activity might be of use as a predictor of the effect of adjuvant 5'DFUR on breast cancer.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biotransformation
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / enzymology*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / surgery
  • Chemotherapy, Adjuvant*
  • Chromatography, High Pressure Liquid
  • Disease-Free Survival
  • Female
  • Floxuridine / administration & dosage
  • Floxuridine / pharmacokinetics*
  • Floxuridine / therapeutic use
  • Fluorouracil / metabolism
  • Follow-Up Studies
  • Humans
  • Lymphatic Metastasis
  • Mastectomy, Radical
  • Menopause
  • Middle Aged
  • Mitomycin / administration & dosage
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / metabolism
  • Pentosyltransferases / analysis*
  • Pentosyltransferases / metabolism
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics*
  • Prodrugs / therapeutic use
  • Pyrimidine Phosphorylases
  • Tamoxifen / administration & dosage
  • Thymidine Phosphorylase / analysis*
  • Thymidine Phosphorylase / metabolism
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Hormonal
  • Neoplasm Proteins
  • Prodrugs
  • Floxuridine
  • Tamoxifen
  • Mitomycin
  • Pentosyltransferases
  • Pyrimidine Phosphorylases
  • Thymidine Phosphorylase
  • Fluorouracil
  • doxifluridine