BMC Cancer 2009, 9:154 http://www.biomedcentral.com/1471-2407/9/154 (TTP_BD) and overall survival (OS) were estimated by Kaplan-Meier analysis and compared using the log-rank test. Cox proportional hazard model was used to identify the independent predictive factors that significantly influ- enced the overall survival of patients with metastatic bone disease. The proportionality assumption for the Cox regression and the log rank test was checked and verified by using the log-log plot. All P values were 2-tailed, with 5% significance levels. All statistics were calculated using SPSS® 13.0 software (SPSS Inc., Chicago, IL, USA). Results Baseline characteristics Among 317 patients with bone metastases at diagnosis, 262 (82.6%) patients were treated with BPs during follow- up. The median number of cycles of BP treatment was 17.7 (range, 3 to 57 cycles), and the median interval between cycles was 31 days. Patients' characteristics are shown in Table 1. Types of BP were zoledronate (27.5%), pamidronate (40.1%), and ibandronate (0.8%). Eighty- three (31.6%) patients received more than one type of BP, sequentially. Aside from more weight bearing bone involvement (P < 0.001), the BP group had better prog- nostic factors, such as HR positivity (P < 0.001), negative HER2 receptors (P = 0.035), fewer visceral metastases (P = 0.002), bone only metastases (P = 0.014), and fewer met- astatic sites (P = 0.006), compared to the non-BP group. There was no significant difference in use of anti-HER2 therapy between BP and non-BP groups. The log-log plot showed that the proportionality assump- tion was satisfied (data not shown). Although the rate of progression of bone disease and the incidence of SREs (except for the first event) were higher in the BP group, there was no statistical difference in the time to progres- sion of the bone disease (TTP_BD) according to BP treat- ment (P = 0.059). The overall survival (OS) was significantly longer in the BP group (Fig. 1). In the univariate analysis, the following factors, in addi- tion to BP treatment, showed positive association with longer survival: HR positivity, HER2 negativity, disease free interval (DFI) > 2 years, sum of metastatic sites < 3, and no visceral involvement (Table 2). Among these fac- tors, HR positivity, DFI > 2 years, and no visceral metasta- sis were significant in multivariate Cox analysis. Table 1: Characteristics of total patients with metastatic bone disease Factors Age, median years (range) PS** (ECOG ≥ 2) Pre-menopausal Post-menopausal ER***/PR† positive HER2 positive DFI‡ (month, median, range) Initial stage IV Adjuvant treatment Radiotherapy Chemotherapy Hormonal therapy Metastatic sites Visceral (liver, lung) LNs§ Soft tissue Bone only Weight bearing bone involvement Sum of metastatic sites (range) Cycles of palliative chemotherapy 1 2 ≥ 3 Palliative AI¶ use Palliative anti-HER2 therapy Disease progression in bone (n) SREs (except the first event) BP group N = 262 45.5 (25–77) 10/166 (6.0%) 79/176 (44.9%) 97/176 (55.1%) 202 (77.1%) 72 (27.5%) 25 (0–230) 61 (23.4%) 111 (42.4%) 176 (67.2%) 127 (48.5%) 116 (44.3%) 119 (45.4%) 78 (29.8%) 81 (30.9%) 225 (86.2%) 2 (1–6) 36 (13.7%) 53 (20.2%) 157 (59.9%) 168 (64.1%) 58/72 (80.6%) 97 (47.8%) 63 (27.2%) Non-BP group N = 55 50 (30–68) 2/27 (7.4%) 7/30 (23.3%) 23/30 (76.7%) 28 (50.9%) 23 (41.8%) 21 (0–174) 11 (20%) 27 (49.1%) 38 (69.1%) 21 (38.2%) 37 (67.3%) 30 (54.5%) 20 36.4%) 8 (14.5%) 25 (45.5%) 3 (1–6) 8 (14.5%) 13 (23.6%) 29 (52.7%) 23 (41.8%) 20/23 (86.9%) 21 (38.2%) 21 (24.7%) P-value|| NS* NS 0.027 < 0.001 0.035 NS NS NS NS NS 0.002 NS NS 0.014 < 0.001 0.006 NS 0.002 NS NS NS Abbreviations:*, not significant; **, performance status; ***, estrogen receptor; †, progesteron receptor; ‡, disease free interval; § lymph nodes; ¶ aromatase inhibitor; ||, P-value was obtained by chi-square test except variables of age and DFI which were obtained through Mann-Whitney U test Page 3 of 9 (page number not for citation purposes)