Serum HER‐2/neu and relative resistance to trastuzumab‐based therapy in patients with metastatic breast cancer
Open Access
- 25 July 2008
- Vol. 113 (6), 1294-1301
- https://doi.org/10.1002/cncr.23689
Abstract
BACKGROUND. Previous reports based on small patient numbers suggested that changes in serum HER‐2/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. Cancer 2008. © 2008 American Cancer Society.Keywords
This publication has 29 references indexed in Scilit:
- Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancerCancer Cell, 2006
- Potential Clinical Utility of Serum HER-2/neu Oncoprotein Concentrations in Patients with Breast CancerClinical Chemistry, 2003
- Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus TamoxifenJournal of Clinical Oncology, 2003
- Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast CancerJournal of Clinical Oncology, 2002
- Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast CancerJournal of Clinical Oncology, 2002
- Assessment of Methods for Tissue-Based Detection of the HER-2/neu Alteration in Human Breast Cancer: A Direct Comparison of Fluorescence In Situ Hybridization and ImmunohistochemistryJournal of Clinical Oncology, 2000
- Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.Journal of Clinical Oncology, 1996
- Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian CancerScience, 1989
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987
- Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptorNature, 1986