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

Autor: Ali SM; Department of Hematology-Oncology, Penn State Hershey Cancer Center, Penn State University/Hershey Medical Center, Hershey, Pennsylvania 17033, USA., Carney WP, Esteva FJ, Fornier M, Harris L, Köstler WJ, Lotz JP, Luftner D, Pichon MF, Lipton A
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2008 Sep 15; Vol. 113 (6), pp. 1294-301.
DOI: 10.1002/cncr.23689
Abstrakt: 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 >or=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 (>or=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.
((c) 2008 American Cancer Society.)
Databáze: MEDLINE
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