PYRIMIDINE NUCLEOSIDE PHOSPHORYLASE-ACTIVITY AND 5-FLUOROURACIL CONCENTRATION IN TISSUE FROM BREAST-CANCER PATIENTS AFTER ADMINISTRATION OF5'-DEOXY-5-FLUOROURIDINE

To better understand the mechanism of action of the chemotherapeutic a gent 5'-deoxy-5-fluorouridine (5'-DFUR), we attempted to establish his topathologically whether a correlation exists between pyrimidine nucle oside phosphorylase (PyNPase) activity, 5-fluorouracil (5-FU) concentr ation in breast tissue, and the antitumor effects of 5'-DFUR. Ninety-n ine patients with breast cancer received oral 5'-DFUR for 1 week preop eratively at daily doses of 600 mg (group A), 800 mg (group B), and 12 00 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 can cer tissue, involved lymph nodes, and normal lymph nodes than in norma l 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 tha n 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 s howed little or no improvement. Although these findings were not stati stically significant, they suggest that the level of PyNPase activity may be directly related to the antitumor effect of 5'-DFUR.