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Published on: August 1, 2018
FGFR1 Antibody Validation and Characterization of FGFR1 Protein Expression in ER+ Breast Cancer
Paula I Gonzalez-Ericsson1, Alberto Servetto2, Luigi Formisano3
1Breast Cancer Research Program, Vanderbilt Ingram Cancer Center.
Abstract:
Clinical trials in patients with ER+ breast cancer with or without FGFR pathway somatic alterations have shown limited clinical benefit from treatment with FGFR tyrosine kinase inhibitors alone or in combination with endocrine therapy. This is likely because of an inadequate predictive biomarker to select appropriate patients. In this study, we evaluated 4 anti-FGFR1 antibodies in breast cancer cell lines and patient-derived xenografts with FGFR1 amplification. We correlated D8E4 expression in 209 tumors from postmenopausal patients with stage I-III operable ER+ breast cancer with FGFR1 amplification status as determined by fluorescence in situ hybridization. FGFR1 amplification was identified in 10% of tumors (21/209), 80% of which exhibited membranous FGFR1 expression; however, only 50% of amplified cases showed strong, complete membranous staining (3+) based on established criteria to score HER2 by immunohistochemistry. These findings suggest the combined evaluation of FGFR1 status by immunohistochemistry and fluorescence in situ hybridization may need to be incorporated into the selection of patients for trials with FGFR inhibitors.
Insights
Identifying a better biomarker for FGFR inhibitors in ER+ breast cancer is crucial. This study found that combining FGFR1 amplification and specific protein expression may improve patient selection for targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clinical trials with FGFR tyrosine kinase inhibitors in ER+ breast cancer have yielded limited benefits.
- Inadequate predictive biomarkers hinder patient selection for FGFR inhibitor therapies.
Purpose of the Study:
- To evaluate anti-FGFR1 antibodies in breast cancer models with FGFR1 amplification.
- To correlate D8E4 expression with FGFR1 amplification status in ER+ breast cancer patients.
Main Methods:
- Tested 4 anti-FGFR1 antibodies in breast cancer cell lines and patient-derived xenografts.
- Assessed FGFR1 amplification using fluorescence in situ hybridization (FISH).
- Correlated D8E4 expression with FGFR1 amplification in 209 ER+ breast cancer tumors.
Main Results:
- FGFR1 amplification was found in 10% of tumors.
- 80% of amplified tumors showed membranous FGFR1 expression.
- Only 50% of amplified cases displayed strong (3+) membranous staining.
Conclusions:
- Combined evaluation of FGFR1 status (FISH and immunohistochemistry) may be necessary for patient selection.
- This approach could improve the efficacy of FGFR inhibitor trials.
- D8E4 expression shows potential as a predictive biomarker for FGFR inhibitors.
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