Objective: Since skeletal related events (SRE) worsen QOL, the information relating to the SRE is important in the patient's care. We have examined the incidences of bone metastasis (BM) and SRE in Japan and explored the prognostic factors which may affect the BM or SRE free period or survival.

Patients and Methods: A retrospective, multicenter (21 institutes) study was performed. Patients with node positive or node negative with moderate to severe recurrence risk primary breast cancer were included. The primary endpoint was SRE-free period, and the secondary endpoints were BM-free period and the over-all survival period. By using a proportional hazard model (Cox regression), factors which affect these endpoints were examined in the population excluding stage IV patients.

Results: 1,779 patients were registered and 1,708 patients' data were used for analysis. The median follow-up duration was 5.71 years. SRE occurred in 133 (68.9%) of 193 patients who developed BM. The median SRE-free period from the initial treatment was 1,006 days. The SRE-free rate and SRE-free survival rate at 5-years were 92.6% and 85.4%, respectively. The median period from the initial SRE to the second one was 112 days, and the second to the third one was 147 days. The median BM-free period was 767 days. The BM-free and BM-free survival rates at 5-years were 89.2% and 83.7%, respectively. The over-all survival rate at 5-years was 89.4%. The SRE-free period was significantly affected by the number of lymph node metastasis (LN mets) (Hazard Ratio; HR [95%CI]; 1.09 [1.042–1.143], p = 0.0002) and clinical stage (when stage I was assumed as reference, HR in stage II; 4.54 [1.296–15.933], stage III; 7.36 [1.171–31.539], p = 0.0262). SRE-free survival period was affected by the number of LN mets (HR; 1.10 [1.066–1.131], p < 0.0001), stage (stage I as reference, HR in stage II: 2.93 [1.349–6.349], and stage III: 4.28 [1.694–10.815], p = 0.008), and tumor phenotype (Luminal [L] A as reference, HR in LB; 1.89 [0.868–4.117], L-HER2: 2.81 [1.334–5.923], HER2: 2.68 [1.266–5.659], Triple negative (TN); 5.38 [3.031–9.537], p < 0.0001). The BM-free period was affected by the number of LN mets (HR; 1.09 [1.048–1.125], p < 0.0001), stage (stage I as reference, HR in stage II; 3.24 [1.219–8.619], stage III; 6.37 [2.080–19.485], p = 0.0045), and BMI (HR; 0.92 [0.854–0.987], p = 0.0213). BM free-survival period was affected by the number of LN mets (HR;1.10 [1.067–1.129], p < 0.0001), stage (stage I as reference, HR in stage II; 2.80 [1.344–5.825], stage III; 4.43 [1.853–10.609], p = 0.0037), phenotype (LA as reference, HR in LB; 2.23 [1.097–4.534], L-HER2; 3.10 [1.557–6.191], HER2; 2.57 [1.344–5.324], TN; 5.02 [2.887–8.738], p < 0.0001), and BMI (HR; 0.92 [0.872–0.981], p = 0.0090). Over-all survival period was affected by the number of LN mets (HR; 1.11 [1.075–1.147], p < 0.0001), stage (stage I as reference, HR in stage II; 2.32 [1.000–5.381], stage III; 4.24 [1.551–11.573], p = 0.01777), and phenotype (LA as reference, HR in LB; 2.26 [0.850–6.013], L-HER2; 3.58 [1.393–9.184], HER2; 4.22 [1.719–10.347], TN; 10.05 [4.810–21.004], p < 0.0001).

Conclusion: Tumor phenotype appears to have an impact on SRE-free, BM-free and overall survival period, but not on SRE-free and BM-free period.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-04.