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

Suhail M. Ali, Walter P. Carney, Francisco J. Esteva, Monica Fornier, Lyndsay Harris, Wolfgang J. Köstler, Jean Pierre Lotz, Diana Luftner, Marie France Pichon, Allan Lipton, Kim Leitzel

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1294-1301
Number of pages8
JournalCancer
Volume113
Issue number6
DOIs
StatePublished - Sep 15 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Ali, S. M., Carney, W. P., Esteva, F. J., Fornier, M., Harris, L., Köstler, W. J., Lotz, J. P., Luftner, D., Pichon, M. F., Lipton, A., & Leitzel, K. (2008). Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer. Cancer, 113(6), 1294-1301. https://doi.org/10.1002/cncr.23689