BC-DETECT: combined detection of serum HE4 and TFF3 improves breast cancer diagnostic efficacy.

Abstract

Early accurate breast cancer (BC) diagnosis is critical in disease management. Mammography has been widely used. However, its radiation, and high false-negative and -positive results have always been a concern. We evaluated combined detection of human epididymal protein 4 (HE4) and trefoil factor 3 (TFF3) as substitute method to enhance BC diagnosis. HE4 and TFF3 blood levels were determined by ELISA in sera of 120 BC patients and 80 women (40 healthy and 40 benign breast disease) as controls. Receiver-operating characteristic curve was applied for evaluation diagnostic power of each biomarker and their combination. In BC patients, serum HE4 [5 (2-11.9) vs. 3.1 (1.8-5.4) and 1 (1-3.5); P = 0.022] and TFF3 [5.3 (4.5-6.7) vs. 4.7 (4-4.8) and 3.9 (3-4.4); P = 0.027] were significantly higher than that in benign and healthy groups, respectively. Both HE4 (AUC = 0.783; P < 0.0001) and TFF3 (AUC = 0.759; P < 0.0001) had superior BC diagnostic ability compared to CEA and CA-15.3. Logistic regression analysis revealed simplified index BC-DETECT = HE4 + TFF3, and its values were significantly (P = 0.0132) elevated in BC (10.9 (8.4-17.2) compared to benign (7.2 (5.4-10.1)) and healthy (5.1 (4-6.3)) controls. AUC of BC-DETECT for BC prediction was (AUC = 0.850; P < 0.0001) with sensitivity, specificity, and positive and negative predictive values and accuracy of 84.2%, 70%, 80.8%, 74.7%, and 78.5%, respectively. High BC-DETECT levels were associated with tumor non-luminal subtypes, late stage, high grade, large size, lymph-node invasion, and multiple lesions. BC-DETECT is inexpensive, rapid, and easy to perform and reliably guides BC early detection. Moreover, the association between elevated BC-DETECT values and disease severity may propose its potential role as prognostic marker.