Pyrimidine nucleoside phosphorylase activity and 5-fluorouracil concentration in tissue from breast cancer patients after administration of 5′-deoxy-5-fluorouridine

Abstract

To better understand the mechanism of action of the chemotherapeutic agent 5′-deoxy-5-fluorouridine (5′-DFUR), we attempted to establish histopathologically whether a correlation exists between pyrimidine nucleoside phosphorylase (PyNPase) activity, 5-fluorouracil (5-FU) concentration in breast tissue, and the antitumor effects of 5′-DFUR. Ninety-nine patients with breast cancer received oral 5′-DFUR for 1 week preoperatively at daily doses of 600 mg (group A), 800 mg (group B), and 1200 mg (group C). PyNPase activity and 5-FU concentration were measured in tumors, neighboring normal breast tissue, and axillary lymph nodes with or without metastases. PyNPase activity was higher in breast cancer tissue, involved lymph nodes, and normal lymph nodes than in normal breast tissue. 5-FU concentrations were also higher in tumor tissue than in normal mammary gland tissue in all three groups. In the lymph nodes, 5-FU concentrations were higher in patients with metastases than in those without metastases. Of the 89 evaluated patients, 12 (13.5%) showed histologic improvement. PyNPase activity was higher and 5-FU concentrations were lower in the improved patients than in those who showed little or no improvement. Although these findings were not statistically significant, they suggest that the level of PyNPase activity may be directly related to the antitumor effect of 5′-DFUR.