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


CONCLUSIONS
Intratumoral PyNPase activity might be of use as a predictor of the effect of adjuvant 5'DFUR on breast cancer.
Hata
Y
Y
Sapporo Social Insurance General Hospital, Japan.
Takahashi
H
H
Sasaki
F
F
Ogita
M
M
Uchino
J
J
Yoshimoto
M
M
Akasaka
Y
Y
Nakanishi
Y
Y
Sawada
Y
Y
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002851:Chromatography, High Pressure Liquid; D018572:Disease-Free Survival; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005472:Fluorouracil / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D015409:Mastectomy, Radical; D008593:Menopause; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D010430:Pentosyltransferases / Q000032:analysis* / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D057845:Pyrimidine Phosphorylases; D013629:Tamoxifen / Q000008:administration & dosage; D013939:Thymidine Phosphorylase / Q000032:analysis* / Q000378:metabolism; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D011355:Prodrugs; D005467:Floxuridine; D013629:Tamoxifen; D016685:Mitomycin; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine