Adjuvant bisphosphonates in breast cancer treatment

Several solid tumors like breast cancer tend to spread to the bone, where the microenvironment is especially receptive to the tumor by special interactions between bone cells and tumor cells. Bone metastases often lead to skeletal-related events with significant morbidity and mortality. The therapy of bone metastases and osteoporosis with bisphosphonates (BPs) has been established many years ago as a standard treatment. In the adjuvant setting, cancer treatment-induced bone loss is a frequent cause of morbidity, and prevention and treatment of this condition with BPs and the monoclonal antibody denosumab are also well established. Besides postmenopausal patients, several studies including 2 larger studies by the Austrian Breast and Colorectal Cancer Study Group (ABCSG) and the Cancer and Leukemia Group B (CALGB) have shown an increase in bone mineral density in premenopausal women. BPs as anticancer treatment are, however, still controversial because several studies yielded conflicting results, with beneficial effects only in subgroups of patients. The publication of the latest Oxford overview of prospective trials is being awaited; at the presentation of the results, a 34% relative reduction of bone metastasis and a 17% improvement in overall survival was demonstrated in the subgroup of postmenopausal patients. These results will likely lead to an incorporation of the use of BPs into routine adjuvant breast cancer treatment.