HE4 elevated levels correlated with breast cancer progression

Background: Despite several, there were many Breast Cancer (BC)- related deaths around the world. Searching for new analytical tools for BC detection at early stages is widely demanded. Aim: We aimed to evaluate Human Epididymal Protein 4 (HE4) clinical value in BC development and progression. Methods: HE4 serum levels were determined by ELISA in females with BC (n=120), benign breast disease (n=40) and healthy women (n=40). Receiver operating characteristic curve was applied for evaluation HE4 diagnostic power. Results: In BC patients, HE4 [5 (2-11.9) vs. 3.1 (1.8-5.4) and 1 (1- 3.5); P=0.022] was significantly higher than that in benign and healthy females, respectively. Compared to CEA and CA-15.3, it had superior diagnostic ability (AUC=0.783; P<0.0001; 73.3% sensitivity; 63.7% specificity). This ability increase when comparing BC patients to only healthy controls (AUC=0.862; 73.3% sensitivity; 77.5% specificity). Elevated HE4 levels were associated disease progression including multiple lesions, late stages, high grades, large size, lymph node invasion and non-luminal molecular subtypes. Spearman correlation analysis revealed that HE4 high levels significantly (P<0.05) correlated with tumor stage, histological grade and tumor size. Conclusions: HE4 is inexpensive, rapid, easy to perform and reliably BC biomarker. Moreover, its association with disease severity may support its potential role as prognostic BC marker.