Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer

BACKGROUND. Previous reports based on small patient numbers suggested that changes in serum HER-21/neu levels may predict response or lack of response to trastuzumab-based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER-2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff. METHODS. This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first-line trastuzumab-based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER-2/neu decrease ≥20% (receiver operating curve analysis) was defined as a significant HER-2/neu change. RESULTS. Of the 307 patients with MBC, 191 patients (62%) had a significant decline (<20%) in serum HER-2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER-2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER-2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P < .0001), longer duration of response (369 days vs 230 days; P =.008), and longer overall survival (898 days vs 593 days; P <.018). CONCLUSIONS. In this pooled analysis of 307 patients with MBC, individuals who did not achieve a significant decline (≥20%) in serum HER-2/neu levels had decreased benefit from trastuzumab-based therapy, and these patients should be considered for clinical trials evaluating additional HER-2/neu-targeted interventions.