Circulating HER2 mRNA-positive cells in the peripheral blood of patients with stage I and II breast cancer after the administration of adjuvant chemotherapy: evaluation of their clinical relevance

Background: The purpose of this study was to evaluate the prognostic value of circulating tumor cells (CTCs) expressing HER2 messenger RNA (mRNA) after the administration of adjuvant chemotherapy in women with operable breast cancer. Patients and methods: HER2 mRNA-positive CTCs were detected by nested RT-PCR in the peripheral blood of 214 patients with stage I and II breast cancer after the completion of adjuvant chemotherapy. Results: HER2 mRNA-positive CTCs were detected in 45 (21%) patients. Adjuvant chemotherapy could eliminate HER2 mRNA-positive CTCs in 16 (30.2%) prechemotherapy-positive patients. Moreover, HER2 mRNA-positive CTCs were detected in eight (5%) of 161 prechemotherapy-negative patients. The detection of HER2 mRNA-positive CTCs after chemotherapy was associated with reduced disease-free interval (DFI) (P = 0.006) but not with overall survival (P = 0.2); this effect was mainly observed in node-negative patients (P = 0.04) and to a lesser extent in node-positive (P = 0.06). Multivariate analysis revealed that the detection of HER2 mRNA-positive CTCs was an independent predictive factor for DFI (hazard ratio 3.238, P < 0.0005). Conclusions: The detection of HER2 mRNA-positive CTCs after the completion of adjuvant chemotherapy may provide clinically useful information concerning the efficacy of treatment and the prognosis of patients with operable breast cancer.