Abstract
Epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis. The emerging role of treatments co-targeting the EGFR system in breast cancer has increased the need to identify companion biomarkers. The aim of this study is to investigate whether pretreatment serum levels of EGFR and EGFR ligands in early-stage breast cancer patients might provide prognostic information as a stepping stone for further investigation. The study, which included 311 early-stage breast cancer patients, investigated associations between preoperative serum levels of EGFR and EGFR ligands (epidermal growth factor, heparin-binding epidermal growth factor (HBEGF), amphiregulin, transforming growth factor-α and betacellulin) and survival. Cutoffs were determined using Youden’s method, and overall survival (OS) and invasive disease-free survival (IDFS) were evaluated using Cox regression. Preoperative S-EGFR < 60.3 ng/mL was associated with shorter OS and IDFS in both univariate analyses and when adjusting for standard prognostic factors (p < 0.05). Preoperative S-HBEGF < 21.4 pg/mL was associated with shorter OS in both univariate and multivariate analyses, whereas association with shorter IDFS could only be demonstrated in the univariate analysis. In conclusion, our study demonstrated shorter survival in early-stage breast cancer patients who had low pretreatment levels of either S-EGFR or S-HBEGF.
Highlights
Epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis
The present study investigated the prognostic value of EGFR and EGFR ligands in the serum of 311 patients with early-stage breast cancer and demonstrated significantly shorter survival in patients with low pretreatment levels of either Serum levels of EGFR (S-EGFR) or S-heparin-binding epidermal growth factor (HBEGF)
S-EGFR below the defined cut-off at 60.3 ng/mL was associated with shorter overall survival (OS) and invasive disease-free survival (IDFS) in both univariate and multivariate analysis in the entire population
Summary
Epidermal growth factor receptor (EGFR) and its ligands are involved in cancer pathogenesis. The emerging role of treatments co-targeting the EGFR system in breast cancer has increased the need to identify companion biomarkers. The study, which included 311 early-stage breast cancer patients, investigated associations between preoperative serum levels of EGFR and EGFR ligands (epidermal growth factor, heparin-binding epidermal growth factor (HBEGF), amphiregulin, transforming growth factor-α and betacellulin) and survival. Our study demonstrated shorter survival in early-stage breast cancer patients who had low pretreatment levels of either S-EGFR or S-HBEGF. We conducted a systematic review to investigate whether EGFR and EGFR ligands might serve as prognostic or predictive blood-based biomarkers in breast cancer[16]. The prognostic and predictive significance of EGFR and EGFR ligands as blood-based biomarkers in early-stage breast cancer remains undetermined
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