Denosumab and the current status of bone-modifying drugs in breast cancer

Abstract

Background. Bone-modifying therapy is a primary research interest in breast cancer. Several features contribute to the importance of the bone environment in the management of breast cancer. Firstly, bone metastases represent the most common site of breast cancer metastases and secondly, the emergence of cancer treatment-induced bone loss (CTIBL) among breast cancer survivors and patients is of increasing concern. Furthermore, concordant with the “seed and soil” theory, agents that alter the bone microenvironment may even prevent tumor cell seeding in bone and limit cancer growth. Material and methods. Medical databases and conference proceedings were searched to identify articles, abstracts and clinical trials that have or are investigating denosumab and bisphosphonates in cancer therapy. Our search included a predefined focus on bone-modifying therapies in early and advanced breast cancer. Results and discussion. Bisphosphonates (BPs) have an established role both in the prevention and treatment of CTIBL and have been studied in the adjuvant setting for early breast cancer (EBC). Denosumab is a monoclonal antibody directed against RANK ligand and thereby inhibits osteoclastogenesis and bone resportion. It is the newest agent approved for the treatment of postmenopausal osteoporosis and the prevention of skeletal-related events (SRE) in cancer patients with solid tumors and bone metastases. Denosumab has a favorable toxicity profile in comparison to BPs and has the potential to improve cancer outcomes. Conclusion. This review examines the existing role of denosumab in the treatment of bone complications of breast cancer and its potential role as adjuvant therapy.

Acknowledgements

We would like to thank Mauro Martino for his assistance with Figure 1 preparation. Paul Goss is supported by the Avon Foundation, New York. Paul Goss is the Chair of the D-Care clinical trial. None of the authors have any conflicts of interest to disclose.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Notice of Correction

The Early Online version of this article published online ahead of print on 12 Dec 2012 contained an error on page 5. The reference “64” should have read “66” in Table 1.

This has been corrected for the current version.