Molecular Detection and Prognostic Value of Circulating Cytokeratin-19 Messenger RNA–Positive and HER2 Messenger RNA–Positive Cells in the Peripheral Blood of Women with Early-Stage Breast Cancer

Abstract

Purpose The aim of this study was to evaluate the clinical relevance of the simultaneous detection of cytokeratin (CK)–19 messenger RNA (mRNA)– and HER2 mRNA–positive cells in peripheral blood of women with early-stage breast cancer. Patients and Methods CK-19 mRNA– and HER2 mRNA–positive cells were detected using a real-time and a nested reverse-transcriptase polymerase chain reaction assay, respectively, in a cohort of 185 women with early-stage breast cancer before the initiation of any adjuvant systemic treatment. Detection of CK-19 mRNA– and HER2 mRNA–positive cells in the peripheral blood was correlated with clinical outcome. Results Overall, 63 of the 185 patients (34%) had detectable CK-19 mRNA–positive cells, and 33 (52.3%) also had detectable HER2 mRNA–positive cells. Patients with CK-19/HER2 mRNA–negative cells showed a trend toward longer disease-free survival (DFS) compared with patients with CK-19 mRNA–positive/HER2 mRNA–negative cells ( P = .054) and had longer DFS than patients with CK-19/HER2 mRNA–positive cells ( P < .001). Similarly, overall survival (OS) was higher in patients with CK-19/HER2 mRNA–negative cells compared with patients with CK-19 mRNA–positive/HER2 mRNA–negative cells ( P = .039) or CK-19/HER2 mRNA–positive cells ( P < .001). Patients with CK-19/HER2 mRNA–positive cells had shorter DFS but not OS compared with patients with CK-19 mRNA–positive/HER2 mRNA–negative cells. In multivariate analysis, the simultaneous detection of CK-19 mRNA– and HER2 mRNA–positive cells was independently associated with early relapse. Conclusion The simultaneous detection of CK-19 mRNA– and HER2 mRNA–positive cells in peripheral blood predicts poor clinical outcome for women with early-stage breast cancer.