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The clinical relevance of circulating tumor cells in correlation to other serum biomarkers (VEGF, HER2, EGFR, TIMP1, CAIX, RASp21) in patients with metastatic breast cancer
20 September 2018 (online)
Presence of circulating tumor cells (CTCs) predicts impaired survival in metastatic breast cancer (MBC). This study was designed to evaluate whether serum biomarkers, such as HER2, VEGF, EGFR, TIMP1, CAIX and RASp21, provide additional prognostic information.
253 MBC patients were enrolled in this prospective, multicentre study. Serum was collected before first-line or later-line treatment. Serum biomarkers were quantified by commercially available ELISA, CTCs using CellSearch.
Presence of ≥5CTCs/7.5 ml blood was associated with elevated sHER2, TIMP1, CAIX and lower sEGFR levels. Elevated sVEGF correlated with ER-positivity, higher therapy line, elevated RASp21 and TIMP1. Elevated sHER2 was associated with HER2-positive tumor, elevated CAIX and TIMP1, visceral metastasis and multiple metastatic sites. Patients with elevated TIMP1 were more likely to present with elevated CAIX and lower sEGFR. No associations were observed between RASp21 and clinical-pathological factors. In the univariate survival analysis, presence of ≥5CTCs, elevated levels of sHER2, sVEGF, RASp21, TIMP1 and CAIX as well as low levels of sEGFR predicted shorter overall survival (OS) while CTC-positivity, elevated sVEGF, RASp21, TIMP1 and CAIX were associated with shorter progression-free survival (PFS). In the multivariate analysis including classical clinical-pathological prognostic parameters and serum biomarkers, CTC status, RASp21, grading and line of therapy predicted OS, while CTC status, line of therapy, ER-status and sVEGF were associated with PFS.
All biomarkers considered were associated with survival in the univariate analysis. However, when CTC status was taken into account, only RASp21 remained independent predictor of OS while only sVEGF predicted PFS. Our results support the biological role of these proteins in breast cancer.