Different prognostic value of cytokeratin-19 mRNA-positive circulating tumor cells according to estrogen receptor status in early breast cancer

Abstract

10500 Background: We have previously shown that the detection of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) predicts poor clinical outcome in node-negative breast cancer patients. Here, we examined the prognostic value of CK-19 mRNA-positive CTCs in early breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) status. Methods: We analysed peripheral blood from 448 consecutive patients with stage I-III breast cancer after surgery and before the initiation of any adjuvant treatment for the presence of CK-19 mRNA-positive CTCs using a real-time RT-PCR assay. The effect of CK-19 mRNA-positive CTCs on clinical outcome of patients with ER-positive, ER-negative, and triple-negative (ER/PR/HER2-negative) tumors was investigated. Results: CK-19 mRNA-positive CTCs were detected in 181 (40.4%) of the 448 patients; 109 (41.5%) of 263 patients with ER-positive, 71 (40.6%) of 175 patients with ER-negative and 27 (35%) of 77 patients with triple-negative tumors. There was no significant difference in the proportion of patients with detectable CK-19 mRNA-positive CTCs in the ER-negative and ER-positive subgroups (p=0.856). After a median follow-up of 53 months, patients with CK-19 mRNA-positive CTCs experienced reduced disease-free survival (DFS) (p<0.0005) and overall survival (OS) (p<0.0005); this was mainly observed in patients with ER-negative (p<0.0005 and p<0.0005, respectively) and triple-negative (p=0.008 and p=0.001, respectively) but not with ER-positive (p=0.174 and p=0.364, respectively) tumors. In multivariate analyses, detection of CK-19 mRNA-positive CTCs was the strongest independent prognostic factor associated with reduced DFS and OS in the entire cohort (p<0.0005 and p=0.009, respectively), in ER-negative (p<0.0005 and p=0.003, respectively) and triple-negative (p=0.020 and p=0.022, respectively) but not in ER-positive tumors (p=0.350 and p=0.621, respectively). Conclusions: Detection of CK-19 mRNA-positive CTCs predicts poor clinical outcome at five years follow-up, only in patients with ER-negative and triple-negative, but not with ER-positive, early breast cancer. No significant financial relationships to disclose.