Abstract
Overexpression of epidermal growth factor receptor in breast cancer is associated with estrogen receptor negativity, higher histological grade and larger tumors. The aim of the present study was to evaluate the clinical significance of serum EGFR (sEGFR) in relation to circulating tumor cells (CTCs) in metastatic breast cancer. 252 patients were enrolled in this prospective multicentre study. Blood was drawn before start of a new line of therapy. sEGFR was determined using a sandwich-type ELISA. CTCs were detected using CellSearch. sEGFR was determined in 48 healthy controls and 252 patients, with no significant differences between the two groups. Clinical-pathological parameters did not correlate with sEGFR, irrespective of the cutoff chosen. Patients with sEGFR levels above the 50th and 75th percentile were more likely to present with <5 CTCs per 7.5 ml blood (p = 0.007; p = 0.003). Patients with sEGFR ≥73 ng/ml had significantly longer overall survival than those with sEGFR <73 ng/ml (19.7 vs. 15.2 months; p = 0.007). In the multivariate analysis, presence of ≥5 CTCs, higher grading and higher line of therapy remained independent predictors of shorter OS, while only higher line of therapy and presence of ≥5 CTCs were independent predictors of shorter PFS.
Highlights
The family of erbB receptors consists of four closely related transmembrane proteins involved in a network of signalling pathways that have been shown to play a major role in malignant transformation of various epithelial tumors[1,2,3,4]
HER2 was overexpressed by the primary tumor and/or metastasis in 35% of patients; the majority of patients (70%) had a hormone receptor positive tumor. 49.8% of patients presented with ≥ five circulating tumor cells (CTCs) per 7.5 ml of peripheral blood
We found similar serum epidermal growth factor receptor (EGFR) (sEGFR) values in healthy controls and breast cancer patients with a median value of 60.35 and 62.00 ng/ml, respectively
Summary
The family of erbB receptors consists of four closely related transmembrane proteins (erbB1, erbB2, erbB3, erbB4) involved in a network of signalling pathways that have been shown to play a major role in malignant transformation of various epithelial tumors[1,2,3,4]. While evidence exists to support HER2 activity to be directly linked to enhanced mobility and invasiveness of cancer cells, data on the clinical relevance of the first discovered protein of the erbB family, the erbB1 receptor, is less conclusive[5]. Since all erbB receptors share a similar structure containing an extracellular ligand-binding domain (ECD) that may be shed from the cell surface into the blood stream, attempts have been made to measure EGFR levels in the serum using enzyme-based assays and evaluate its clinical utility as a biomarker[16,17,18]. The aim of the present study was to evaluate the clinical significance of sEGFR levels in relation to the CTCs in a large cohort of metastatic BC patients
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