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The role of EGFR amplification in trastuzumab resistance: A correlative analysis of TBCRC003

Authors :
Carla I. Falkson
Ingrid A. Mayer
Carlos L. Arteaga
K. Josephs
Julie Najita
Elizabeth Claire Dees
EP Winer
Nan Lin
Ian E. Krop
Mothaffar F. Rimawi
Antonio C. Wolff
Timothy J. Hobday
Rita Nanda
Ludmila Flores
Source :
Journal of Clinical Oncology. 29:528-528
Publication Year :
2011
Publisher :
American Society of Clinical Oncology (ASCO), 2011.

Abstract

528 Background: To identify mechanisms of resistance to trastuzumab (T), we developed and characterized T-resistant HER2+ breast cancer (BC) cell lines; these lines acquired EGFR amplification and were sensitive to both lapatinib (L) and gefitinib. To validate this finding, we prospectively assessed EGFR copy number in circulating tumor cells (CTC) from patients (pts) on TBCRC003, a multicenter clinical trial of L and T. Methods: Pts with measurable, HER2+ metastatic BC (MBC) were eligible. Cohort 1: No prior T, L, or chemotherapy (CT) for MBC, and > 1 yr from adjuvant T, if received. Cohort 2: 1-2 prior lines of CT for MBC, including T, or relapse within 1 yr of adjuvant T. Pts received L 1,000 mg QD + T (2 mg/kg weekly or 6 mg/kg Q3W). CTC were collected using a modification of the CellSearch Profile Kit (Veridex) at baseline, 4wk, and progression. CTC were analyzed by FISH for EGFR and CEP7 and amplification was defined as EGFR/CEP7≥2. Results: EGFR amplification was present in CTC at baseline in 11/39...

Details

ISSN :
15277755 and 0732183X
Volume :
29
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........4ae804a66c0ee03af03e59bd7b974f7d
Full Text :
https://doi.org/10.1200/jco.2011.29.15_suppl.528