Treatment of Breast Cancer with 5-Fluorouracil

THE ROLE OF 5-FLUOROURACIL i n the chemotherapy of breast cancer has yet to be accurately defined. That it is useful and effective in some cases is beyond doubt, but its associated toxicity renders it a for-midable agent to use. For some years, metabolic differences be-tween normal and neoplastic tissues have been sought with the hope that such dif-ferences could be exploited by chemothera-peutic agents. Both Rutman (1) and Heidelberger (2), with their co-workers, have observed that uracil may be preferen-tially utilized for synthesis of nucleic acid in certain neoplastic tissues. Consequently, several altered molecules of uracil were synthesized and their effects on tumor growth studied (3, 4). 5-Fluorouracil has proved to be the most widely used and most valuable of these agents to date. Altering the uracil molecule by replac-ing a hydrogen atom with a fluorine atom in the 5 position prevents the normal utilization of uracil in nucleic acid pro-duction. The altered molecule (or one of its metabolites) blocks the enzyme thymi-dylate synthetase, essential for the methyla-tion reaction which is necessary for the formation of thymine, thereby producing thymine deficiency. The ultimate effect is interference with the efficient and sufficient production of deoxyribonucleic and ribo-nucleic acids (5, 6). This, in turn, prevents normal cell growth and division. The effects of 5-fluorouracil are most marked in those cells that grow rapidly,