RELATIONSHIP OF ELEVATED TUMOR THYMIDINE PHOSPHORYLASE IN NODE-POSITIVE BREAST CARCINOMAS TO THE EFFECTS OF ADJUVANT CMF

Background. Thymidine phosphorylase (TP) catalyses the reversible phos phorylation of thymidine to thymine and 2-deoxyribose-1-phosphate. Hig h expression of TP in cell lines potentiates the effects of the cytoto xic drugs 5-fluorouracil and methotrexate, both of which are used in t he cyclophosphamide, 5-fluorouracil and methotrexate (CMF) treatment r egimen of breast cancer. Patients and methods. We therefore examined t he expression of this enzyme in 328 invasive breast carcinomas using i mmunohistochemistry and assessed whether the expression of this enzyme by the tumour predicts patient response to CMF in node-positive patie nts. Results: Whereas no significant difference in either relapse-free survival (RFS) (P = 0.2) or overall survival (OS) (P = 0.07) was obse rved between TP-negative and -positive rumours 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-neg ative tumours. A multivariate analysis of the 134 node-positive patien ts demonstrated that in ductal carcinomas, TP was an independent varia ble for OS, Conclusions: This pilot study suggests that patients with TP-positive rumours have a significant survival benefit when treated w ith CMF and supports the hypothesis that TP enhances tumour sensitivit y to the anti-metabolites 5-fluorouracil and methotrexate.