Περίληψη:
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.
Συγγραφείς:
Cheng, H.
Ballman, K.
Vassilakopoulou, M.
Dueck, A. C. and
Reinholz, M. M.
Tenner, K.
Gralow, J.
Hudis, C. and
Davidson, N. E.
Fountzilas, G.
McCullough, A. E.
Chen, B.
and Psyrri, A.
Rimm, D. L.
Perez, E. A.
