Diagnostic value of serum HER2 levels in breast cancer: a systematic review and meta-analysis

Amir Shamshirian,Reza Alizadeh-Navaei,Keyvan Heydari,George W Yip,Amir Reza Aref,Majid Ebrahimi Warkiani,Zeinab Hamzehgardeshi,Mahmood Moosazadeh,Sajad Razavi Bazaz,Danial Shamshirian

doi:10.1186/s12885-020-07545-2

Abstract

BackgroundMeasurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. We aimed to undertake a systematic review and meta-analysis focusing on the diagnostic/screening value of serum HER-2 levels in comparison to routine methods.MethodsWe performed a systematic search via PubMed, Scopus, Cochrane-Library, and Web of Science databases for human diagnostic studies reporting the levels of serum HER-2 in breast cancer patients, which was confirmed using the histopathological examination. Meta-analyses were carried out for sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR).ResultsFourteen studies entered into this investigation. The meta-analysis indicated the low sensitivity for serum HER2 levels (Sensitivity: 53.05, 95%CI 40.82–65.28), but reasonable specificity of 79.27 (95%CI 73.02–85.51), accuracy of 72.06 (95%CI 67.04–77.08) and AUC of 0.79 (95%CI 0.66–0.92). We also found a significant differences for PPV (PPV: 56.18, 95%CI 44.16–68.20), NPV (NPV: 76.93, 95%CI 69.56–84.31), PLR (PLR: 2.10, 95%CI 1.69–2.50) and NLR (NLR: 0.58, 95%CI 0.44–0.71).ConclusionOur findings revealed that although serum HER-2 levels showed low se nsitivity for breast cancer diagnosis, its specificity, accuracy and AUC were reasonable. Hence, it seems that the measurement of serum HER-2 levels can play a significant role as a verification test for initial negative screening test results, especially in low-income regions due to its cost-effectiveness and ease of implementation.

Highlights

Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients
The cut-off value was set at 15.0 ng/ml for serum-HER2 concentration in most of the studies, according to the Food and Drug Administration (FDA) and various manufacturer’s recommendations for breast cancer
Seven studies used chemiluminescence immunoassays (CLIA), five studies used Enzyme-Linked Immunosorbent Assay (ELISA), and two studies used both methods for the determination of serum-HER2 levels

Summary

Introduction

Measurement of serum human epidermal growth factor receptor-2 (HER-2/neu) levels might play an essential role as a diagnostic/screening marker for the early selection of therapeutic approaches and predict prognosis in breast cancer patients. Previous investigations showed that the early detection and diagnosis of this malignancy could lead to promising treatment and improve the chance of successful therapy [4]. In this regard, there are different types of diagnostic approaches for the detection of breast cancer, such as magnetic resonance imaging (MRI) of the breast, mammography, molecular imaging, biopsy, and ultrasound tomography [5]. Slamon et al [8] have understood the importance of HER-2 as a diagnostic factor for breast cancer in 1987 This protein has gained significant attention as a biomarker as well as a target of diagnosis, prognosis, and therapy in breast cancer patients [9]

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