The Thrombogenic Effect of Anticancer Drug Therapy in Women with Stage II Breast Cancer

Thromboembolic disease has long been recognized as a complication of cancer. Recent reports have suggested that drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may contribute to this risk, but it has not been possible to separate the effect of these drugs from that of the cancer. We performed a randomized trial comparing 12 weeks of chemohormonal therapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, doxorubicin, and tamoxifen) with 36 weeks of chemotherapy (using cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in patients with Stage II breast cancer. Among 205 patients randomly assigned to treatment, there were 14 episodes of thrombosis (6.8 percent). These 14 episodes occurred during 979 patient-months of chemotherapy; by comparison, there were no events during 2413 patient-months without therapy. During the first 12 weeks of the study, five patients in the 12-week group and four patients in the 36-week group had thrombosis. During the subsequent 24 weeks, when only patients in the 36-week group were still receiving chemotherapy, there was no thrombosis in the 12-week group, but there were five additional events in the 36-week group (P = 0.03). These findings suggest that chemotherapy contributes to thrombosis in patients with breast cancer. (N Engl J Med 1988; 318:404–7.) THROMBOEMBOLIC disease has long been recognized as a complication of cancer. 1 Recent reports indicate that some drugs used in the treatment of cancer, including chemotherapeutic agents and hormones, may also induce thrombosis, 2 , 3 but the relative contributions of anticancer drugs and cancer itself to thrombogenesis have not been clearly determined. Ideally, differentiation between these two potential thrombogenic factors requires that the rates of thrombosis in patients with a similar tumor burden be compared during periods with and without drug therapy. Women with Stage II breast cancer who receive adjuvant anticancer drug therapy are a particularly appropriate group in which to assess . . .