HRU resulting from SREs is
HRU resulting from SREs is of increasing relevance in times of financial and economic restraint because it can help to determine the financial burden to hospital managers and payers. A separate analysis of the costs associated with SREs in this study found that the most costly SRE, spinal cord compression, had a mean cost per SRE of €4884–€12,082, and costs per surgery to bone ranged from €3348 to €9407. Pathologic fracture and radiation to bone had slightly lower costs per SRE (€1015–€6968 and €704–€2461, respectively) but still represented a considerable financial burden . Treatments that delay or prevent SREs could help to reduce the utilization of healthcare resources, thereby lowering the costs associated with metastatic bone disease. Historically, intravenously administered bisphosphonates, such as zoledronic acid, have been the mainstay of treatment for the prevention of SREs in adult patients with advanced malignancies involving the bone . More recently, the RANK ligand inhibitor denosumab has been widely approved for the prevention of SREs in adults with bone metastases from solid tumors  after it was demonstrated to be superior to zoledronic mu receptor antagonist in an integrated analysis of patients with solid tumors from three identically designed, phase 3, head-to-head clinical trials . The systemic treatments enzalutamide, abiraterone acetate and radium-223 dichloride, currently only available for use in patients with metastatic castration-resistant prostate cancer, have shown a trend towards delayed bone complications compared with placebo in phase 3 trials [21–23]. In these studies, concomitant use of bone-targeted agents was permitted and preliminary data demonstrated a further trend towards improved outcomes in patients who received additional bone-targeted therapy. As bone outcomes were not a primary focus for these studies, the extent to which these new agents protect against SREs should be further assessed [23–25].
Conflict of interest
Acknowledgments The authors would like to acknowledge the contributions of all study 20060392 (STARS) investigators, study teams and patients. Editorial support was provided by Oxford PharmaGenesis™. Funding for this support was provided by Amgen (Europe) GmbH.
Introduction Breast cancer is the leading cause of cancer among adult U.S. women, with over 200,000 new cases estimated to have occurred in 2013 . Treatment strategies have included both endocrine and cytotoxic therapies, with tamoxifen and aromatase inhibitors as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer . Treatment with aromatase inhibitors has been associated with accelerated bone loss and increased fracture risk [3–10], prompting greater attention towards bone health and fracture outcomes in women with breast cancer. Other factors contributing to greater fracture risk in women with breast cancer include estrogen deficiency, chemotherapeutic regimens, nutritional status, frailty, local cytokine factors and metastatic bone disease [7,9,11–13]. Melton et al. studied 608 women with invasive breast cancer in Olmsted County, Minnesota, and found that the overall risk of fracture was elevated 1.8-fold, although the relative risk was only 1.2 after exclusion of pathologic and incidentally discovered fractures . This study, conducted among women with breast cancer diagnosed in 1990–1999 followed for up to 15 years, found that various breast cancer therapies were associated with increased fracture risk, with the strongest associations seen for pathologic fracture . The Women׳s Health Initiative found a 1.5-fold increased risk of hip fracture in postmenopausal women with breast cancer and an even higher risk among those treated with aromatase inhibitors . Compared to tamoxifen, aromatase inhibitor therapy has been associated with a 3- to 4-fold increased risk of hip fracture [3,4].