Serum Human Epididymis Protein-4 (HE4) - A novel Approach to Differentiate Malignant from benign Breast Tumors

BACKGROUND: The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. METHODS: Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. RESULTS: A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. CONCLUSION: Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.