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Treatment and Prevention of Bone Metastases from Breast Cancer: A Comprehensive Review of Evidence for Clinical Practice
Department of Medical Oncology, Royal North Shore Hospital, St. Leonards NSW 2065, Sydney, Australia
Sydney Medical School, University of Sydney, Camperdown NSW 2050, Sydney, Australia
Department of Medical Oncology, Gosford Hospital, Gosford NSW 2250, Australia
* Author to whom correspondence should be addressed.
Received: 9 November 2013; in revised form: 11 December 2013 / Accepted: 16 December 2013 / Published: 9 January 2014
Abstract: Bone is the most common site of metastasis from breast cancer. Bone metastases from breast cancer are associated with skeletal-related events (SREs) including pathological fractures, spinal cord compression, surgery and radiotherapy to bone, as well as bone pain and hypercalcemia, leading to impaired mobility and reduced quality of life. Greater understanding of the pathophysiology of bone metastases has led to the discovery and clinical utility of bone-targeted agents such as bisphosphonates and the receptor activator of nuclear factor kappa-B ligand (RANK-L) antibody, denosumab. Both are now a routine part of the treatment of breast cancer bone metastases to reduce SREs. With regards to prevention, there is no evidence that oral bisphosphonates can prevent bone metastases in advanced breast cancer without skeletal involvement. Several phase III clinical trials have evaluated bisphosphonates as adjuvant therapy in early breast cancer to prevent bone metastases. The current published data do not support the routine use of bisphosphonates in unselected patients with early breast cancer for metastasis prevention. However, significant benefit of adjuvant bisphosphonates has been consistently observed in the postmenopausal or ovarian suppression subgroup across multiple clinical trials, which raises the hypothesis that its greatest anti-tumor effect is in a low estrogen microenvironment. An individual patient data meta-analysis will be required to confirm survival benefit in this setting. This review summarizes the key evidence for current clinical practice and future directions.
Keywords: breast cancer; bone metastases; bisphosphonates; denosumab; skeletal-related events; adjuvant; randomized controlled trials; meta-analysis
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Li, B.T.; Wong, M.H.; Pavlakis, N. Treatment and Prevention of Bone Metastases from Breast Cancer: A Comprehensive Review of Evidence for Clinical Practice. J. Clin. Med. 2014, 3, 1-24.
Li BT, Wong MH, Pavlakis N. Treatment and Prevention of Bone Metastases from Breast Cancer: A Comprehensive Review of Evidence for Clinical Practice. Journal of Clinical Medicine. 2014; 3(1):1-24.
Li, Bob T.; Wong, Matthew H.; Pavlakis, Nick. 2014. "Treatment and Prevention of Bone Metastases from Breast Cancer: A Comprehensive Review of Evidence for Clinical Practice." J. Clin. Med. 3, no. 1: 1-24.