Acquired protein C deficiency in patients with breast cancer receiving cyclophosphamide, methotrexate, and 5-fluorouracil

Recent reports have documented an increase of thrombotic complications in patients with carcinoma of the breast receiving chemotherapy regimens containing cyclophosphamide, methotrexate, and 5-fluorouracil. The authors studied blood from nine such patients screening for abnormalities that might predispose to thrombosis or indicate that the coagulation cascade had been activated. Six of the patients were in the adjuvant setting, and three had metastatic disease. Samples were collected from each patient before, during, and after completion of the chemotherapy in question. In each patient a statistically significant decline in functional protein C activity (P = 0.001) was demonstrated at midtherapy. In seven of nine patients functional protein C level normalized after the cessation of therapy. No other positive results were found. The authors conclude that the combination of cyclophosphamide, methotrexate, and 5-fluorouracil, when administered to patients with a diagnosis of carcinoma of the breast, causes a reversible decline in the activity of protein C.