[Bisphosphonates in the adjuvant therapy of breast cancer-- pathophysiology, animal models, and clinical experiences].

Bisphosphonates have been used successfully for many years in the treatment of hypercalcemia and to reduce skeletal-related complications of metastases. Their mechanism of action is based on alterations of the microenvironment of metastatic cells (apoptosis of osteoclasts, effects on adhesion molecules, etc.). Animal experiments have repeatedly shown that early use of bisphosphonates can prevent the occurrence of new metastases, an effect that is enhanced by cytotoxic therapy. Initial results from two clinical trials are now available that confirm this prophylactic effect in patients with breast cancer. About 700 women received 1,600 mg of clodronate per day orally for 2 years, and 700 women were randomized to a control group. A significant reduction in bone metastases was seen in both studies, and one study also showed a reduction in the occurrence of visceral metastases.