Evaluation of serum epidermal growth factor receptor (EGFR) in correlation to circulating tumor cells in patients with metastatic breast cancer

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.

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

“…While soluble forms of such proteins as HER2, VEGF and CAIX can be detected in peripheral blood and elevated levels have been shown to influence prognosis, the currently most widely examined biomarker in metastatic BC are CTCs 41,42 . We have previously shown that serum proteins HER2, VEGF and EGFR predict survival in univariate analysis but lose their prognostic significance in multivariate analysis when CTC status is taken into account as well 38,43,44 . In contrast, we found that elevated levels of serum uPA predicted shorter overall survival both in univariate (p < 0.001) and multivariate (p = 0.015) analysis, showing for the first time that circulating uPA is an independent prognostic factor in metastatic BC.…”

“…CTCs were detected using the CellSearch™ system (Veridex LLC, NJ, USA) as described previously 38,43,44,58 . Briefly, 7.5 ml peripheral blood were collected into CellSave Tubes and processed according to manufacturer’s instructions.…”

Dysregulated EGFR pathway in serum in early-stage breast cancer patients: A case control study

“…Disease related up-or downregulation of EGFR and EGFR ligands in blood in breast cancer has been investigated in several case-control studies. Most studies, however, included few study participants and report contradictory results [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] . Few of these studies reported data on newly diagnosed breast cancer patients 18,19,[23][24][25][26] .…”

Prognostic impact of serum levels of EGFR and EGFR ligands in early-stage breast cancer

“…In conclusion, the results of the present study indicate shorter survival in patients with low S-EGFR not only in metastatic breast cancer as shown in previous studies, but also in early-stage breast cancer. Several potential mechanisms explaining the associations between low S-EGFR and shorter survival have been proposed and were discussed thoroughly in a study by Banys-Paluchowski 28 . However, current evidence is inconclusive, and further investigations into these mechanisms are recommended.…”

“…Several studies have investigated the prognostic significance of S-EGFR in metastatic breast cancer patients 16 , 28 . Overall, the results of these studies indicate associations between low levels of S-EGFR and shorter survival 17 – 19 , 28 . Though some studies found no significant associations, no studies reported opposing results 16 .…”