Evaluation of 5-fluorouracil related genes in breast cancer to predict the effect of adjuvant therapy with oral fluorouracil derivatives

New anticancer drugs have been developed, and prediction of their effect is needed to perform tailor made chemotherapy. We investigated a selection of the predictive markers for oral adjuvant chemotherapy among 5-fluorouracil (5-FU) related genes. 5-FU related genes were examined by using a laser captured microdissection and real-time RT-PCR in 220 patients with invasive breast cancer. Sixty-six patients were treated with postoperative oral fluorouracil derivatives for 12 months or more, and we examined the prognosis of these patients according to the expression of 5-FU related genes. The median of thymidylate synthase (TS), dehydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyltransferase (OPRT) mRNA values in the 220 specimens were determined for cut-off levels separating low and high gene expression. In 66 patients, 5-year disease-free survival (DFS) in the TP-high group (n=28) was significantly better than that in the TP-low group (n=38) (P=0.016). Of 220 patients, the 69 patients in TP-high group comprised 28 patients treated with oral fluorouracil derivatives and 41 patients with hormone therapy alone. The proportion of patients with lymph node involvement in the fluorouracil group was significantly greater than that in the hormone therapy alone group (P=0.003). Five-year DFS was not significantly different between the groups (P=0.80). Our results suggest that adjuvant oral fluorouracil chemotherapy may improve the prognosis of the patients with TP high expression breast cancer, and TP mRNA level in breast cancer may predict the effect of new oral fluorouracil derivatives for postoperative adjuvant chemotherapy.