EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial

Autor: E. A. Perez, C. Hudis, J. Gralow, N. E. Davidson, A. E. McCullough, M. M. Reinholz, Amylou C. Dueck, B. Chen, David L. Rimm, K. Tenner, M. Vassilakopoulou, G. Fountzilas, H. Cheng, Karla V. Ballman, A. Psyrri
Rok vydání: 2013
Předmět:
Cancer Research
Disease free survival
Receptor
ErbB-2
Breast Neoplasms
Pharmacology
Antibodies
Monoclonal
Humanized
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Breast cancer
breast cancer
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols
medicine
Biomarkers
Tumor
Humans
Epidermal growth factor receptor
immunofluorescence assay
Survival rate
030304 developmental biology
0303 health sciences
integumentary system
biology
business.industry
Follow up studies
Middle Aged
medicine.disease
3. Good health
Egfr expression
ErbB Receptors
Survival Rate
tumour biomarker
Oncology
Tissue Array Analysis
030220 oncology & carcinogenesis
biology.protein
Cancer research
Clinical Study
Female
Antibody
business
epidermal growth factor receptor
medicine.drug
Follow-Up Studies
Zdroj: British Journal of Cancer
ISSN: 1532-1827
Popis: Background: Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial. Methods: Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130). Results: Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28–3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073). Conclusions: High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy.
Databáze: OpenAIRE
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