Skeletal-related events (SREs) in breast cancer patients with bone metastases treated in the nontrial setting

Clinical trials exploring bisphosphonate (BP) use in patients with bone metastases from breast cancer (BC) consistently state skeletal-related event (SRE) rates > 50%. These trials predominantly include patients with bone only disease, and also frequently use screening radiology to detect asymptomatic fractures. Both these variables are likely to increase the incidence of SREs and thereby overestimate BP benefit. Little data exists regarding the natural history of SREs among patients treated with i.v. BPs in the nontrial setting. Charts from two institutions (PMH and CVH) were reviewed to determine predictive risk factors for SRE development post i.v. pamidronate therapy in BC patients with bone metastases. Eighty-seven charts from 1999 to 2005 with complete outcome data were identified and reviewed. Pain was the most common presentation for bone metastases occurring in 49 women (56%). At diagnosis, 31 patients (35%) had bone only disease, and 57 (65%) had concomitant visceral metastases. Twenty-nine patients (33%) experienced an SRE prior to commencing BP treatment. Thirty-three women (38%) subsequently developed an SRE after a median of 5 BP treatments. SREs included radiation (79%), pathologic fractures (12%), and hypercalcemia (9%). On Cox regression, baseline history of osteoporosis (HR = 2.8; p = 0.045) and the presence of bone only disease (HR 3.0; p = 0.003) were predictive of SRE development. In patients with and without osteoporosis, median time to SRE was 305 and 866 days, respectively (p < 0.001). The frequency of SREs in this study was significantly lower than that reported in clinical trials of i.v. BP use. The lower incidence of SREs in this setting could affect sample size calculations for future event-driven BP trials. While the greatest risk of SREs despite BP therapy appears to be in patients with osteoporosis and with metastatic disease confined to the skeleton, further prospective study is merited to confirm and characterize the impact of these risk factors on SRE development.