A preliminary study on dihydropyrimidine dehydrogenase activity in breast cancer

We studied dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS), key enzymes in regulating the pharmacokinetics and chemosensitivity to 5-FU, in 36 breast cancer patients as a control group and 18 patients as a 5-FU group, in which 5-FU was given orally for 2 weeks before surgery at a dose of 200 mg/day. Cancer tissues with adjacent normal tissue were sampled and stored until the assay. The DPD activity and TS amount were determined according to the radio-enzymatic assay and radiobinding assay, respectively. The DPD activity was significantly higher in breast cancer than in the adjacent breast tissue. This finding was observed in T1 and T2, node negative and ER positive breast cancers in the control group as well as in the 5-FU group. The DPD activity in T3 was significantly lower than in T1, and that of the adjacent breast tissue in T3 was significantly higher than in T1; therefore, the tumoral/non-tumoral ratio of DPD activity was significantly lower in T3 than T1. TS was significantly elevated in both groups, without significant differences. The clinical implication of elevated DPD activity in T1, T2, node negative or ER positive breast cancer compared to the respective normal breast tissue activity remains to be studied, because it is still unclear whether or not the tumoral DPD activity regulates the local concentration of 5-FU within the tumor. The amount of TS and DPD activity was not influenced by the oral administration of 5-FU for 2 weeks at the dose of 200 mg/day.