Expression of epidermal growth factor receptor (EGFR) in blood and tumor in patients with breast carcinoma: Prognostic analysis.
Authors: De Araujo Rogerio Agenor , da Luz Felipe Andrés Cordero , Marinho Eduarda da Costa , Nascimento Camila Piqui , Marques Lara de Andrade , Delfino Patricia Ferreira Ribeiro , Antonioli Rafael Mathias , Araújo Breno Jeha , Silva Ana Cristina Araújo Lemos da , Monteiro Maria Luiza Gonçalves dos Reis , Neto Morun Bernardino , Silva Marcelo José Barbosa 
Published: June 2021

e15013

Background: EGFR acts on tumor progression and can be quantified in the blood (bEGFR) and in the tumor (tEGFR). This study analyzed the impact of these biomarkers on overall survival (OS) in different subtypes of breast carcinoma (BC). Methods: Prospective study with 214 patients with BC and 89 women with normal mammography and without a history of cancer (control), matched by age. All signed the free and informed consent form. Blood collection for bEGFR analysis, detected by the ELISA method using the R&D Systems DY231 kit, was performed before surgery (stages I and II; 80 patients), before neoadjuvant chemotherapy (CHT) (stages II and III; 103 patients) or before palliative CHT (stage IV; 31 patients). The material for analysis of tEGFR was from tumor biopsy, before any treatment, by immunohistochemistry using Dako clone 31G7. Continuous Kaplan-Meier analysis and Cox regression were used for statistical tests. Statistical significance was established at p < 0.05. Results: At an average follow-up of 35.40 months (±15.65 months), 50 deaths occurred in an average time of 20.92 months (±11.80 months). The control group showed significantly higher bEGFR (p < 0.0005) [40.45 ng/ml (18.10 – 117.15 ng/ml)] than the BC group [29.90 ng/ml (4.78 – 100.85 ng/ml)]. There was no correlation between tEGFR and bEGFR (Spearman's rho of -0.022). There was no impact on OS (p = 0.518) according to the negativity (0%) or positivity (≥1%) of tEGFR. Tumors with negative estrogen receptor (ER), compared to positive ER, showed higher expression of tEGFR (p < 0.0001). No significant differences were found between high and low expression of bEGFR in patients Luminal A (n = 45; p = 0.588), Luminal B (n = 79; p = 0.742) or in positive HER2 (n = 38; p = 0.7520). Patients with Triple Negative BC (TN) (n = 46) and bEGFR ≤47.8 ng/ml had a higher OS [29.1 months (6.63 – 62.4)] than patients with bEGFR > 47.7 ng/ml [13.36 months (3.66 – 60.43), (p = 0.020)]. In multivariate analysis on TN tumors, covariated with the stage, an increased risk of death was demonstrated by about 330% [HR = 4.301 (1.476 – 12.538), p = 0.008] for patients with bEGFR > 47.8 ng/ml. In initial patients (I + II), covariate with the molecular subtype, an increased risk of death was demonstrated by about 420% [HR = 5,210 (1,237 – 21,948), p = 0.024] for bEGFR > 45.9 ng/ml. There was no significant correlation of bEGFR according to the histological grade of the tumor (G1, G2 or G3), the Ki67 (< or ≥14%) or body mass index. Conclusions: There was no correlation between bEGFR and tEGFR. Increased expression of bEGFR in patients with TN tumors is a significant predictor of lower SG. bEGFR was able to define patients with high and low risk of death in both initial and advanced TN tumors. The methodology for quantifying bEGFR expression is simple and inexpensive. In view of these findings, future studies should evaluate different therapeutic options according of the expression of this biomarker.