Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.

Survival among women with breast cancer improved significantly in a geographically defined population during the period when adjuvant systemic therapy became widely used.

Biweekly paclitaxel and cisplatin is an active combination in the treatment of metastatic breast cancer, including for patients with previous exposure to anthracyclines.

In a number of mammalian species, including man, the 4-amino analogs of pteroylglutamate persist in liver and kidney for many months after administration (1-4). In the rat (3) and mouse (4), the binding site appears to be the enzyme dihydrofolate reductase [also termed folate reductase (5) and tetrahydrofolate dehydrogenase.1] Studies with partially purified dihydrofolate reductase obtained from several sources (6-8) have shown the affinity of this enzyme for the 4-amino analogs to be extremely high.Recent work with tritium-labeled pteroylglutamate in vivo has shown that, in man, the labeled compound can be displaced from cells several days after its administration, both by unlabeled pteroylglutamate (9, 10) and by other compounds that possess an affinity for the enzyme dihydrofolate reductase (11). If, as animal experiments suggest, the 4-amino analogs bind to the same enzyme, a similar procedure should also bring about the displacement of these compounds. The studies reported here show that, in man, tritiated methotrexate (amethopterin; 4-amino-AN10-methylpteroylglutamic acid) can be readily displaced