Abstract P5-16-03: The impact of skeletal-related events on pain interference in patients with advanced breast cancer and bone metastases
Authors: Fallowfield Lesley , Patrick Donald L , Von Moos Roger , Cleeland Charles S , Zhou Ying , Balakumaran Arun , Qian Yi 
Published: May 2015

Abstract
Background: Patients with advanced breast cancer and bone metastases are at an increased risk for experiencing skeletal-related events (SREs), which include pathological fracture (PF), surgery to bone (SB) radiation to bone (RB), and spinal cord compression (SCC). The pain of SREs can be severe enough to interfere with daily functioning. Here we evaluated the impact of SREs on pain interference in patients with advanced breast cancer and bone metastases.
Methods: In a double-blind, double-dummy, placebo-controlled trial, patients were evenly randomized to receive monthly denosumab 120 mg SC or zoledronic acid 4 mg IV, (adjusted for renal function). Pain interference (overall, emotional well-being, and physical function) was assessed at baseline and each study visit using the Brief Pain Inventory-Short Form (BPI-SF) with scores that ranged from 0 (no interference) to 10 (complete interference). A change of ≥ 2 points from baseline was considered clinically meaningful. To evaluate the overall impact of SREs on pain interference, we conducted a post-hoc analysis using a Cox Proportional Hazards model adjusting for SREs as time-dependent covariates and stratified by treatment and randomized stratification factors. The impact of on-study SREs was evaluated using patients’ first on-study SRE, starting 28 days before the SRE occurrence.
Results: 687 first on-study SREs were reported (450 PF, 201 RB, 20 SB, 16 SCC). SCC, RB, and PF were associated with a greater risk of a clinically meaningful increase in overall pain interference (Table 1). For the subdomains, RB and SCC were associated with an increased risk of pain interference with emotional well-being, while PF, RB, and SB were associated with an increased risk of pain interference with physical function.
Impact of on-study SREs on time to ≥ 2-point increase from baseline in pain interference BPI score PFRBSBSCCPain interference - overall (n = 1829) HR (95% CI)1.31 (1.05, 1.63)2.41 (1.80, 3.23)1.85 (0.68, 5.05)4.26 (1.38, 13.19) P value0.0159&lt; 0.00010.23220.0120Pain interference - emotional well being (n = 1806) HR (95% CI)1.20 (0.97, 1.48)2.25 (1.72, 2.95)1.11 (0.41, 3.00)4.74 (2.15, 10.44) P value0.1003&lt; 0.00010.84320.0001Pain interference - physical activity (n = 1690) HR (95% CI)1.35 (1.09, 1.69)2.30 (1.70, 3.10)2.86 (1.09, 7.47)2.26 (0.45, 11.37) P value0.0070&lt; 0.00010.03260.3232Includes patients with baseline BPI score ≤8; HR = hazard ratio; CI = confidence interval.
Conclusions: In patients with advanced breast cancer, SREs are associated with an increase in pain interference. Effective treatments that prevent SREs may reduce the burden of pain on patients’ daily functioning.
Citation Format: Lesley Fallowfield, Donald L Patrick, Roger Von Moos, Charles S Cleeland, Ying Zhou, Arun Balakumaran, Yi Qian. The impact of skeletal-related events on pain interference in patients with advanced breast cancer and bone metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-16-03.