Evaluation for the Clinical Usefulness of Serum HER-2/neu Oncoprotein in Patients with Breast Cancer

Cho, Hyun Jung; Lee, Soo Youn; Kim, Jong Won

Abstract

BACKGROUND
The HER-2/neu oncogene codes a protein of the family of epidermal growth factor receptors and is amplified and/or overexpressed by 20-40% of breast cancers. The extracellular domain (ECD) has a MW of 95-105 kDa and is shed into the blood. We evaluated circulating levels of extracellular domain of HER-2/neu and the clinical usefulness of measuring HER-2/neu in breast cancer patients. METHODS: The serum HER-2/neu levels in patients with primary breast cancer (n=58) were measured by a chemiluminescent method (ADVIA: Centaur TM, Bayer Diagnostics, Chicago, USA) using H2n (Bayer Diagnostics, Chicago, USA) kit. The results were compared with those of age-matched healthy controls (n=59). We evaluated HER-2/neu test for precision and linearity following the guide-lines of NCCLS EP5-A and EP6-P, respectively. The correlation of the circulating HER-2/neu level and the conventional prognostic factors such as tumor size, lymph node involvement, pathologic grade and stage, as well as tumor markers such as CEA, CA 15-3, was studied. We also analyzed ROC curve using several cut-off levels to evaluate the clinical usefulness of serum HER-2/neu concentrations. RESULTS: Serum HER-2/neu levels (mean +/-SD) were increased significantly in breast cancerpatients (10.9 +/-5.4 ng/mL) compared with those of age-matched healthy controls (8.3 +/-2.4 ng/mL, P=0.003). No significant correlations were found between serum HER-2/neu levels and convention-alprognostic indicators of breast cancer including tumor size, lymph node involvement, pathologic grade and stage, and tumor markers including CEA and CA 15-3. CONCLUSIONS: The above findings suggest that serum HER-2/neu ECD quantitation is inadequate as a screening test for breast cancer. Further studies are required to see whether the serum HER-2/ neu test could be employed universally as a substitute for the currently used immunohistochemistry tests or an additional supplementary test for them.