Antiresorptive therapies in oncology and their effects on cancer progression

Bone health is an emerging concern in the early breast cancer setting. Current adjuvant therapies, especially hormonal therapies in premenopausal patients (e.g. goserelin) and aromatase inhibitors in postmenopausal patients, have been associated with substantial decreases in bone mineral density that may place patients at risk for fractures. Bisphosphonates--and the recently approved anti-RANKL antibody, denosumab--have both demonstrated activity for the treatment of postmenopausal osteoporosis and cancer treatment-induced bone loss (CTIBL) in breast cancer patients, although neither has received widespread approval specifically for CTIBL. However, some bisphosphonates, especially the nitrogen-containing bisphosphonate zoledronic acid, have also demonstrated clinically meaningful anticancer effects in patients receiving adjuvant hormonal therapy for breast cancer and in other oncology settings. The effects of denosumab on cancer disease outcomes in the adjuvant setting remain to be established. This discrepancy has created a dilemma in terms of how to evaluate the complete benefit:risk profile of bone-health management options in the adjuvant breast cancer setting. This review summarises the current data on the course of cancer in clinical trials of the antiresorptive agents and provides important insight into the relative anticancer potential of the various therapies.