Prognostic value of baseline serum HER2 extracellular domain level with a cut-off value of 15 ng/mL in patients with breast cancer: a systematic review and meta-analysis.

Purpose: The extracellular domain (ECD) of human epidermal growth factor receptor-2 (HER2) in the blood is a promising biomarker of cancer prognosis and response to therapy, whereas the clinical prognostic role of serum HER2 ECD (sHER2 ECD) level in patients with BC remains controversial. Moreover, its cut-off value significantly varies. Thus, this meta-analysis aimed to quantify the prognostic impact of this biomarker with a specific cut-off value in patients with BC.

Methods: A systematic review of electronic databases was conducted to identify studies that assessed the association between baseline sHER2 ECD level with a cut-off value of 15 ng/mL and clinical outcomes in patients with BC. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS), progression-free survival (PFS), and time to progression (TTP) were the secondary endpoints. An inverse variance random effects meta-analysis was conducted.

Results: Twenty-three studies that included 8231 patients with BC who met the inclusion criteria were included. An elevated baseline sHER2 ECD level was associated with a hazard ratio (HR) of 2.28 (95% confidence interval [CI] 2.00-2.61; P < 0.001) for OS, and this effect was observed in all subgroups. The HRs for an elevated sHER2 ECD level for DFS, PFS, and TTP were 2.52 (95% CI 1.90-3.35; P < 0.001), 1.63 (95% CI 1.37-1.95; P < 0.001), and 1.98 (95% CI 1.66-2.36; P < 0.001), respectively.

Conclusions: An elevated sHER2 ECD level with a cut-off value of 15 ng/mL was associated with poor clinical prognosis in patients with BC. Future studies should be conducted to reduce confounding and explore the mechanism.