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; Felipe Andrés Cordero da Luz; Eduarda da Costa Marinho; Camila Piqui Nascimento; Lara de Andrade Marques; Patrícia Ferreira Ribeiro Delfino; Rafael Mathias Antonioli; Breno Jeha Araújo; Ana Cristina Araújo Lemos da Silva; Maria Luiza Gonçalves Dos Reis Monteiro; Morun Bernardino Neto; Marcelo José Barbosa Silva

doi:10.3332/ecancer.2022.1431

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

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

Authors

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

¹ Federal University of Uberlândia, Avenida Pará, Bloco 2U, 1720, Campus Umuarama, Uberlândia, MG, CEP 38400-902, Brazil.
² Cancer Research and Prevention Nucleus, Grupo Luta Pela Vida, Cancer Hospital in Uberlândia, Uberlândia, MG, CEP 38405-302, Brazil.
³ https://orcid.org/0000-0003-4653-6786.
⁴ https://orcid.org/0000-0002-9381-4913.
⁵ https://orcid.org/0000-0002-1307-9104.
⁶ https://orcid.org/0000-0002-0955-8559.
⁷ https://orcid.org/0000-0002-2734-8352.
⁸ https://orcid.org/0000-0002-2196-9318.
⁹ https://orcid.org/0000-0003-3886-1562.
¹⁰ São Paulo State Cancer Institute of the Medical School of the University of São Paulo, São Paulo, SP, CEP 38405-302, Brazil.
¹¹ https://orcid.org/0000-0003-4892-9911.
¹² https://orcid.org/0000-0002-8220-938X.
¹³ https://orcid.org/0000-0002-7961-6996.
¹⁴ Department of Basic and Environmental Sciences, University of São Paulo, Lorena, SP, CEP 12602-810, Brazil.
¹⁵ https://orcid.org/0000-0003-4292-7800.
¹⁶ Laboratory of Tumor Biomarkers and Osteoimmunology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, CEP 38405-320, Brazil.
¹⁷ https://orcid.org/0000-0002-5807-4286.

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.