Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

Abstract

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylatedRASSF1Aand for global DNA hypomethylation usingLINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylatedRASSF1Agene and the protein markers. Among patients with lower concentrations,RASSF1Acould only be detected periodically. There was discordance between changes of the hypomethylatedLINE-1as compared to the protein markers. Circulating hypermethylatedRASSF1Aand protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.