Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are enzymes involved in the metabolism of 5-fluorouracil (FU). To investigate the relationship of these activities with clinicopathological factors and survival, we measured TS (88 patients) and DPD (122 patients) activities in resected specimens of breast cancer by enzyme assay. Significant difference was found only in TS activity between tumors ≥20 mm in diameter and those <20 mm (p=0.015). There were no significant differences in TS or DPD activity among any other factors. When patients were grouped based on the cut-off levels of TS and DPD activities, 5-year recurrence-free survival rate was 68.8% in the low TS group and 39.7% in the high TS group (p=0.0081), and 50.8% in the low DPD group and 66.5% in the high DPD group (p=0.1627). The Cox proportional hazard model demonstrated that in patients in whom we measured TS activity, significant prognostic factors were nodal status and estrogen receptor (ER) status by univariate analysis, and ER status was also significant by multivariate analysis. In patients in whom DPD activity was measured, the significant prognostic factor was ER status by univariate analysis, and ER and Progesterone receptor (PgR) status by multivariate analysis. These results suggested that TS activity, nodal status and hormone receptors may be possible predictors of clinical outcome in breast cancer, but further investigation on prognostic predictors in 5-FU-based chemotherapy is required.

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