BACKGROUNDMeasurement of human epidermal growth factor receptor 2 (HER2) protein in the serum of metastatic breast cancer patients has previously been reported, but there are no consistent data to support the clinical utility of serum HER2 extracellular domain for patients with early stage breast cancer. We aimed to evaluate the correlation between serum extracellular domain levels and tissue HER2 expression, and analyzed their relationship with clinico-pathological parameters in patients with early stage disease.

METHODSA prospective study was conducted on 232 breast cancer patients with stage I-III prior to treatment. Preoperative serum samples were measured by enzyme-linked immunosorbent assay. Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization assays.

RESULTSThe median serum extracellular domain concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml, with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain levels were reported in 89 patients (38.3%), and HER2-positive expression was observed in 77 patients (33.2%). Multivariate analysis showed that elevated serum extracellular domain correlated with postmenopausal status (P < 0.001), high histological grade (P < 0.001), negativity of both estrogen (P = 0.012) and progesterone receptors (P < 0.001), and high levels of carcinoembryonic antigen 153 (P = 0.048).

CONCLUSIONSWe recommend that 7.4 ng/ml should be used as the cut-off value when evaluating serum extracellular domain levels in early stage of breast cancer. Patients with high serum extracellular domain levels have a certain clinico-pathological characteristics, may provide a basis for clinical practice.