[The role of adjuvant clodronate therapy for prevention of bone metastasis in breast cancer].

Bisphosphonates are effective against increased bone resorption because they inhibit osteoclast activity. The use of these drugs is well established for the treatment of metastatic breast and other cancers; they reduce skeletal complications, hypercalcemia, bone pain, and metastatic progression and they can improve the overall survival and quality of life. Preclinical observations and early clinical data indicate that early bisphosphonate treatment reduces the incidence and the extent of newly developed metastases in breast cancer. There is considerable interest in determining whether bisphosphonate treatment is to prevent the incidence of bone metastases and associated complications. To date three randomized, controlled clinical trials have examined the effect of long-term use of clodronate (1600 mg/d po.) on the incidence of bone metastases, other metastases, the survival of patients, and the side effects of the study drug as well. All the trials have observed significant reduction of the occurrence of bone metastases, although this reduction was significant only during the medication period. One of the trials mentioned have shown an unexpected reduction in non-osseous metastases, and two of them have revealed significant improvements in the death rates. These promising results need further evaluation by large clinical trials with longer treatment periods to establish the clinical role of adjuvant bisphosphonate treatment of primary breast cancer.