A comparative clinical evaluation of the assay of serum extracellular domain of HER2 protein using a chemiluminescent immunoassay method in breast cancer patients with or without HER2 protein expression in immunohistochemistry

Abstract

Objective: The human epidermal growth factor receptor type 2 (HER2) protein has been used as a biomarker for breast cancer. A new method based on chemiluminescent immunoassay for measuring the serum levels of the extracellular domain of HER2 protein (sHER2-ECD) has been developed. Its clinical usefulness has not been clearly established. We studied the clinical usefulness of sHER2-ECD in monitoring breast cancer patients.

Methods: We examined the clinical effectiveness of sHER2-ECD using the ADVIA Centaur XP System in comparison with conventional tumor markers (CA15-3 and CEA) in 148 patients with breast cancer with or without trastuzumab treatment.

Results: The positive rate for sHER2-ECD, CA15-3, and CEA in trastuzumab patients (36) was 25.0%, 19.4%, and 16.7%, and that in non-trastuzumab patients (112) was 20.5%, 22.3%, and 22.3%, respectively. Twenty-three out of 112(20.5%) non-trastuzumab patients were found positive for sHER2-ECD in spite of the negative IHC. Measurement of sHER2-ECD and CA15-3 showed no difference in the expression profile among different clinical stages. During long-term observation in patients negative for HER2 protein by immunohistochemistry, sHER2-ECD was found to be a relatively sensitive indicator of metastasis to distant organs, such as liver and bone, as compared with CA15-3.

Conclusion: sHER2-ECD testing may be a useful tumor marker for monitoring breast cancer patients, even in those with negative IHC for the HER2 protein.