Purpose: The HER2 oncogene encodes a transmembrane tyrosine kinase receptor. This molecule could be a new marker for prognosis and response to therapy in patients with advanced breast cancer. However, the extracellular domain of c-erbB-2 (HER2) transmembrane receptor undergoes proteolytic cleavage from the fulllength protein by metalloproteases, and is shed into the blood as a circulating antigen. To determine the clinical utility of this oncoprotein, the soluble form of HER2 was assayed in the serum of breast cancer patients.
Patients and methods: Serum levels of breast carcinoma antigens CA 15-3 and HER2 were determined in 60 patients, 40 with localized (group A) and 20 with metastatic (group B) breast carcinoma. CA 15-3 measurements served as "gold standard" to which HER2 diagnostic and/or prognostic value was compared. Sera from 10 healthy women served as controls.
Results: Serum levels of the tested tumor markers HER2 and CA 15-3 were significantly higher in cancer patients compared to controls. CA 15-3 correlated with bulky initial tumor, whereas HER2 showed no differences between healthy individuals and group A patients. The serum levels of the tested markers in group B patients were significantly higher (p <0.001) than the serum levels of patients in group A. Striking increase in serum levels of HER2 was found in 52.7% and CA 15-3 in 52.9% of patients with metastatic cancer. A combination of markers was more sensitive than using one marker alone. In this regard, 90% of the patients with metastasis had at least one of the markers increased.
Conclusion: The results of this study suggest that the HER2 oncoprotein may be potentially useful in detecting recurrence of breast cancer. However, to improve sensitivity and specificity in the diagnosis and monitoring of breast cancer, the use of multiple tumor markers should be employed.