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. 2022 Jul 20:16:1431.
doi: 10.3332/ecancer.2022.1431. eCollection 2022.

Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker

Rogério Agenor de Araújo  1   2   3 , Felipe Andrés Cordero da Luz  2   4 , Eduarda da Costa Marinho  2   5 , Camila Piqui Nascimento  2   6 , Lara de Andrade Marques  2   7 , Patrícia Ferreira Ribeiro Delfino  2   8 , Rafael Mathias Antonioli  2   9 , Breno Jeha Araújo  10   11 , Ana Cristina Araújo Lemos da Silva  1   12 , Maria Luiza Gonçalves Dos Reis Monteiro  1   13 , Morun Bernardino Neto  14   15 , Marcelo José Barbosa Silva  16   17
Affiliations

Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker

Rogério Agenor de Araújo et al. Ecancermedicalscience. .

Abstract

Background: Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer.

Methodology: A prospective study of 206 women with breast cancer analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan-Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05.

Results: With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% [hazard ratio (HR): 5.149 (1.900-13.955), p = 0.001] for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index.

Conclusions: Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward.

Keywords: breast cancer; prognosis; sEGFR; tEGFR.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1.
Figure 1.. Boxplot representing the peripheral blood serum EGFR (sEGFR) levels (ng/mL) in (a): healthy volunteers (n = 89) versus breast cancer patients (n = 206) and (b): healthy volunteers versus breast cancer patients (n = 206), according to IH subtype (LA, Luminal A; LB, Luminal B; HER2, HER2/ERBB2 overpexression/amplification; TN, triple-negative).
Figure 2.
Figure 2.. Cumulative survival curves by the KM estimator according to sEGFR levels. (a): Overall survival in the entire cohort (n = 206) and (b): non-TN breast cancer patients (n = 162). Each group was submitted to analysis for establishing the optimal sEGFR level cutoff with prognostic value. Lower sEGFR levels were marginally associated with increased overall survival (blue curve), compared to those with higher levels (red curve), but only in the entire cohort including TN breast cancer patients.
Figure 3.
Figure 3.. Cumulative survival curves by the KM estimator according to sEGFR levels in TN patients (n = 44). Lower sEGFR levels were associated with increased overall survival (blue curve), compared to those with higher levels (red curve).
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