Prognostic Value of the Serum HER2 Extracellular Domain Level in Breast Cancer: A Systematic Review and Meta-Analysis.

Abstract

Simple SummaryWe performed a systematic review and meta-analysis evaluating the predictive value of the serum HER2 extracellular domain (sHER2 ECD) for breast cancer prognosis. Our review investigated 40 studies (12,229 patients) that assessed the impact of the sHER2 ECD levels on breast cancer prognosis and explored the clinical significance of sHER2 ECD levels in different treatment modalities. Our findings indicated that an elevated sHER2 was an unfavorable prognostic factor in breast cancer. More interestingly, sHER2 ECD was found to be a promising biomarker for predicting adverse clinical outcomes of trastuzumab-based treatment but did not affect the efficacy of tyrosine kinase inhibitors. In addition, the baseline cutoff value of sHER2 ECD in different treatment stages of breast cancer remains to be further explored. Overall, our study suggested that sHER2 ECD levels have important prognostic value in breast cancer and may be helpful for clinicians to select the appropriate anti-HER2 therapy for HER2-positive breast cancer, providing more evidence for guiding clinical practice.An elevated serum HER2 extracellular domain is associated with poor prognosis in breast cancer, but the relationship between sHER2 and the efficacy of different modalities remains controversial. Herein, we aimed to evaluate the prognostic value of serum HER2 extracellular domain (sHER2 ECD) in breast cancer and to identify its correlation with the efficacy of different treatment regimens. A systematic search of the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases was conducted to identify studies exploring the association between HER2 ECD level and clinical outcomes among patients with breast cancer. Using the random effects models, pooled hazard ratios (HRs), and odds ratios (ORs) with 95% confidence intervals (CI), were calculated for progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and the objective response rate (ORR). Heterogeneity was further evaluated by subgroup and sensitivity analysis. Overall, 40 studies comprising 12,229 patients were included in this systematic review and meta-analysis. Elevated HER2 ECD levels were associated with worse PFS (HR 1.74, 95% CI 1.40–2.17; p < 0.001), and this effect was observed in patients treated with chemotherapy (HR 1.81, 95% CI 1.37–2.39; p < 0.001), endocrine therapy (HR 1.91, 95% CI 1.57–2.32; p < 0.001), and trastuzumab (HR 1.74, 95% CI 1.31–2.30; p < 0.001). However, this association was not present in patients treated with tyrosine kinase inhibitors (TKIs) (HR 1.44, 95% CI 0.85–2.43, p = 0.17). The HRs/ORs for an elevated HER2 ECD level for DFS, OS, and ORR were 2.73 (95% CI 2.17–3.42; p < 0.001), 2.13 (95% CI 1.77–2.57; p < 0.001), and 0.80 (95% CI 0.49–1.31; p = 0.381), respectively. An elevated sHER2 ECD was an unfavorable prognostic factor in breast cancer but did not affect the efficacy of tyrosine kinase inhibitors such as lapatinib. Detection of sHER2 ECD may be helpful for clinicians selecting the appropriate anti-HER2 therapy for patients with HER2-positive breast cancer.