REDUCTION IN NEW METASTASES IN BREAST-CANCER WITH ADJUVANT CLODRONATETREATMENT

Background Bisphosphonates are effective against the increased bone re sorption caused by certain diseases because they inhibit the activity of osteoclasts. In patients who have breast cancer and metastatic bone disease, the bisphosphonate clodronate (clodronic acid) reduces the f requency of skeletal complications. Experiments in animals and prelimi nary clinical observations indicate that early clodronate therapy redu ces the incidence of new bony metastases in breast cancer. We investig ated the effects of clodronate on the incidence and extent of new meta stases in patients with breast cancer. Methods Between 1990 and 1995, 302 patients with primary breast cancer and tumor cells in the bone ma rrow (the presence of which is a risk factor for the development of di stant metastases) were randomly assigned to receive clodronate at a do se of 1600 mg per day orally for two years (157 patients) or standard follow-up (145 patients). The median length of observation was 36 mont hs. All patients in both groups received standard surgical treatment a nd customary hormonal therapy or chemotherapy. Results Distant metasta ses were detected in 21 patients in the clodronate group and in 42 pat ients in the control group (P<0.001). The incidence of both osseous an d visceral metastases was significantly lower in the clodronate group than in the control group (P=0.003 for both osseous and visceral metas tases). Six patients in the clodronate group died, as did 22 in the co ntrol group (P=0.001), The mean number of bony metastases per patient in the clodronate group was roughly half that in the control group (3. 1 vs. 6.3). Conclusions Clodronate can reduce the incidence and number of new bony and visceral metastases in women with breast cancer who a re at high risk for distant metastases. (N Engl J Med 1998;339:357-63. ) (C)1998, Massachusetts Medical Society.