Toi et al. BMC Cancer 2010, 10:56 http://www.biomedcentral.com/1471-2407/10/56 Table 2 Univariate analysis for overall survival time. Variable Treatment group ER PR Hormone receptor Tumor stage No. of metastatic sites Liver mets Lung mets Bone mets Lymph node mets Brain mets Category trastuzumab/trastzumab+chemo +/- +/- +/- Recurrence/advanced 1/2/3/4 No/Yes No/Yes No/Yes No/Yes No/Yes Hazard ratio 95% C.I. 1.24 0.81 0.45 0.53 3.30 0.54 0.74 0.83 0.42 1.02 0.18 0.43 0.28 0.14 0.19 0.45 0.37 0.34 0.40 0.20 0.49 0.07 3.56 2.33 1.49 1.54 24.4 0.79 1.59 1.72 0.88 2.14 0.46 Page 6 of 10 P-value 0.693 0.694 0.190 0.244 0.242 0.002 0.435 0.615 0.021 0.959 <.0001 Figure 3 Hazard function plots with six-month interval by HER2 expression subgroup. Table 3 Cox regression for survival time using the stepwise variable selection method. Variable Log10HER2 expression (1) Log10HER2 expression (2) Log10HER2 expression (3) Hormone receptor status Brain mets Category 75 percentile~/50~ 75 percentile 25~ 50 percentile/50~ 75 percentile ~ 25 percentile/50~ 75 percentile +/- No/Yes Hazard ratio 95% C.I. 0.25 0.79 0.12 0.18 0.07 0.08 0.32 0.03 0.04 0.02 0.77 1.97 0.51 0.71 0.24 P-value 0.019 0.610 0.004 0.014 <.0001 median value of H2T) sub-groups and using the Cox regression analysis with the continuous H2T value in each of the two subgroups, we found that those patients with higher values for HER2 expression live longer than those with lower values for H2T in the high HER2- expressing group (HR = 0.06, p = 0.010, 95%CI: 0.01- 0.51) (Table 4). In contrast, in the low HER2-expressing group, the opposite trend (those with lower H2T values are favored) was observed (HR = 16.0, p = 0.017, 95%CI: 1.64-155.9). These data suggest that there are two sub- populations of patients in this cohort that behave differ- ently with respect to HER2 expression and OS. Trastuzumab is a remarkably effective drug for patients with breast cancer who over-express HER2, or have evidence of HER2 gene amplification. However, not all patients with MBC respond to trastuzumab, per- haps because not all patients who receive the drug are truly over-expressing HER2, or perhaps because some proportion of those that do over-express HER2 also sig- nal through other pathways that are not antagonized