Relationship of elevated tumour thymidine phosphorylase in node-positive breast carcinomas to the effects of adjuvant CMF.
Fox SB., Engels K., Comley M., Whitehouse RM., Turley H., Gatter KC., Harris AL.
BACKGROUND: Thymidine phosphorylase (TP) catalyses the reversible phosphorylation of thymidine to thymine and 2-deoxyribose-1-phosphate. High expression of TP in cell lines potentiates the effects of the cytotoxic drugs 5-fluorouracil and methotrexate, both of which are used in the cyclophosphamide, 5-fluorouracil and methotrexate (CMF) treatment regimen of breast cancer. PATIENTS AND METHODS: We therefore examined the expression of this enzyme in 328 invasive breast carcinomas using immunohistochemistry and assessed whether the expression of this enzyme by the tumour predicts patients response to CMF in node-positive patients. RESULTS: Whereas no significant difference in either relapse-free survival (RFS) (P = 0.2) or overall survival (OS) (P = 0.07) was observed between TP-negative and -positive tumours in non-treated patients, there was a significant increase in both RFS (P = 0.02) and OS (P = 0.02) in patients treated with CMF in TP-positive compared with TP-negative tumours. A multivariate analysis of the 134 node-positive patients demonstrated that in ductal carcinomas, TP was an independent variable for OS. CONCLUSIONS: This pilot study suggests that patients with TP-positive tumours have a significant survival benefit when treated with CMF and supports the hypothesis that TP enhances tumour sensitivity to the anti-metabolites 5-fluorouracil and methotrexate.