Bisphosphonates in oncology: breast cancer and beyond

Breast cancer frequently spreads to bone and is associated with increased osteoclastic bone resorption. Bisphosphonates exert a powerful inhibitory effect on osteoclast activity and have been shown to reduce the frequency of skeletal complications in patients with breast cancer and metastatic bone disease. Laboratory models have shown that bisphosphonates can reduce the tumor burden in bone. Although improvements in overall survival (the gold standard outcome measure in oncology studies) have been seen in patient subpopulations in many phase III studies of bisphosphonates in breast cancer, only three major trials have been powered to assess overall survival as a primary efficacy endpoint. The results of these studies have been equivocal, a phenomenon largely attributable to methodologic differences in study design and patient selection. Well-designed confirmatory clinical studies are now required to elucidate the true benefits of bisphosphonates in breast cancer. This article discusses future prospects for research with these agents. The benefits and drawbacks of standard clinical parameters and surrogate marker studies are discussed based on experience from past investigations.