Recent studies have demonstrated that
tegafur-
uracil (UFT) is useful for the adjuvant treatment of various types of
cancers. To determine whether
nucleoside metabolizing
enzymes could be used to predict the response to UFT treatment in women with primary
breast cancer, we retrospectively analyzed archived
tumor tissue samples obtained from the 3rd Adjuvant Chemo-Endocrine
Therapy for
Breast Cancer (ACETBC) study, in which adjuvant treatment with
tamoxifen (TAM) plus UFT for 2 years was compared with TAM alone for 2 years. Samples of
tumor tissue were obtained from 192 premenopausal women with node-positive invasive
breast cancer. The tissue samples were examined immunohistochemically to study the expression of
thymidylate synthase (TS),
thymidine phosphorylase (TP), and
dihydropyrimidine dehydrogenase (DPD), as well as the expression of Her2 and p53. In patients with TS-positive
tumors, the risk of relapse was significantly lower in the
tamoxifen plus UFT group than in the
tamoxifen alone group. After 2 years, however, there was a trend towards a decrease in the relative predictive value (RPV) of TS with time. No relationship to outcome was detected for TP or DPD. Expression of Her2 or p53 was a significant prognostic
indicator in the
tamoxifen alone group. TS, but not TP or DPD, may be a useful predictor of response to UFT
therapy. After 2 years, the RPV of TS decreased with time, suggesting that 2 years of treatment with oral
fluorouracil derivatives may be inadequate. Further studies are required to investigate this possibility.