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

Abstract

AimHER2 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. MethodsHER2 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. ResultsHER2 ECD levels were higher in healthy men than in healthy women (medians 12.9ng/mL vs. 9.9ng/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 11.7ng/mL (13.2ng/mL) for the HER2-negative (HER2-positive) patients in the non-metastatic-group (p<0.001) and 11.9ng/mL (16.0ng/mL) in the metastatic-group (p=0.01). Using a cut-off of 30ng/mL the HER2 in tissue was always positive, corresponding to a specificity of 99.8% and a sensitivity of 10.3%. ConclusionsThere 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.