Bone-Targeted Agents and Metastasis Prevention

Abstract

The use of bone-targeted treatments has transformed the clinical care of many patients with metastatic breast cancer. In addition, due to the profound effects of bisphosphonates and denosumab on bone physiology and the bone microenvironment, the potential of bone-targeted agents to modify the process of metastasis has been studied extensively. Many adjuvant trials with bisphosphonates in early breast cancer have been performed. Variable outcomes in terms of disease recurrence have been reported, with any treatment benefits apparently influenced by the age and menopausal status of the patients. The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) conducted a meta-analysis of individual patient data from all available randomised trials to investigate this observation further. This meta-analysis failed to show any benefits of adjuvant bisphosphonates in premenopausal women, but highly significant improvements in bone recurrence (RR = 0.72; 95%CI 0.60–0.86, 2p = 0.0002) and breast cancer mortality (RR = 0.82; 95%CI 0.73–0.93, 2p = 0.002) were seen in the 11,767 postmenopausal women included in the meta-analysis. As a result, clinical guidelines recommend the incorporation of adjuvant bisphosphonates that inhibit osteoclast activity into routine clinical care. Denosumab, which has similar effects on bone cell physiology, appears not to consistently influence disease outcomes, perhaps suggesting that it is the “off target” effects of bisphosphonates on immune function and the biological processes involved in metastasis that are important. Predictive biomarkers beyond menopause are being sought and assessment of the transcription factor MAF (mesenchymal aponeurotic fibrosarcoma gene) appears to identify patients able to benefit from the addition of a bisphosphonate to standard adjuvant anticancer therapies.

A cross-sectional study on Chinese oncology nurses’ knowledge of bone health among cancer patients

“…During weight-bearing or resistance training, the force can be transmitted through the bones and converted into recognizable mechanical signals and cause a series of biochemical reactions to increase bone deposition, thereby increasing bone density and improving osteoporosis in patients [ 37 , 38 ]. Multiple studies [ 30 , 33 , 34 , 39 ] have shown that bone-modifying drugs such as bisphosphonates and denosumab are effective drugs to prevent and treat SREs and CTIBL. This study shows that oncology nurses have insufficient awareness of weight-bearing or resistance training and bone-modifying drugs to prevent bone loss and maintain bone health.…”

Safety and efficacy of exercise in patients with bone metastases: Systematic review and meta-analysis

“…Current therapies for bone metastases are aimed at relieving pain and lowering the risk of fracture in the affected bone. The treatment consists of radiation, bisphosphonates, and RANKL inhibitors [4,5].…”

Daily oral ibandronate with adjuvant endocrine therapy in postmenopausal women with estrogen receptor-positive breast cancer: editorial commentary

“…Bone targeted agents such as the bisphosphonates, which have profound effects on bone cell function and modify the bone microenvironment, have been studied in numerous randomized clinical trials for more than two decades. However, variable results have been observed and the use of adjuvant bisphosphonates in women with early breast cancer remained an area of controversy (2).…”