Serum HER2 supports HER2-testing in tissue at the time of primary diagnosis of breast cancer

Aim: HER2 in tissue is of high prognostic value. Soluble HER2 the extracellular domain (ECD), has been suggested to be a helpful biomarker. We investigated whether there is a relationship between HER2 ECD and HER2 in tissue and whether this relationship could be used for diagnostic purposes. Methods: HER2 ECD was measured in healthy individuals (N = 283, 184 females, 99 males), in patients with history of breast cancer (BC) with no evidence of disease (N = 249) as well as in BC patients before any treatment (N = 565). HER2 in tissue was determined by immunohistochemistry and HER2 ECD was analyzed by immunoassay. Results: HER2 ECD levels were higher in healthy men than in healthy women (medians 12.9 ng/mL vs. 9.9 ng/mL, p < 0.001). We observed an age dependency in women that means the older the women the higher the HER2 ECD level. In treated BC patients there was only a weak difference between younger and older women. For patients without distant metastases as well as patients with metastatic disease we observed a correlation of HER2 in serum and tissue. The median concentrations of HER2 ECD were 11.7 ng/mL (13.2 ng/mL) for the HER2-negative (HER2-positive) patients in the non-metastatic-group (p < 0.001) and 11.9 ng/mL (16.0 ng/mL) in the metastatic-group (p = 0.01). Using a cut-off of 30 ng/mL the HER2 in tissue was always positive, corresponding to a specificity of 99.8% and a sensitivity of 10.3%. Conclusions: There is a strong correlation between HER2 ECD and HER2 in tissue. HER2 ECD supports the HER2 testing in tissue and may reveal false-negative tissue findings. (C) 2013 Elsevier B.V. All rights reserved.