Too much, too little, too late to start again? Assessing the efficacy of bisphosphonates in patients with bone metastases from breast cancer.

The diagnosis of bone metastases can be a devastating occurrence for any woman with breast cancer. In this setting, bone metastases can result in skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, and hypercalcemia. Several trials have confirmed the ability of bisphosphonates to reduce or delay these skeletal complications, and they should now be considered standard care for these women. The analysis of SREs is the typical primary end point in bisphosphonate studies. While not undermining their importance, the definition of SREs does not include complications important to patients, such as pain and immobility. It is these symptoms that are most frequently reported by patients, and bone pain and quality of life (QoL) are often measured as secondary end points in these trials. Bone pain and QoL measures are not standardized and are difficult to compare among patient populations. We do not yet know the true efficacy of bisphosphonates as analgesics or how they impact QoL. This paper reviews the current efficacy measures used in recent bisphosphonate trials and discusses their benefits and limitations. It also explores the role of bone biomarkers and their potential use in monitoring treatment response.