Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer.

Purpose: To evaluate the effect of front-line chemotherapy on CK-19mRNA+ circulating tumor cells (CTCs) and their relevance in patients with metastatic breast cancer (MBC).

Patients And Methods: The presence of CK-19mRNA+ CTCs was assessed using a real-time RT-PCR assay in 298 previously untreated patients with MBC before and after the administration of front-line chemotherapy.

Results: CK-19mRNA+ CTCs were detected in the blood of 199 (66.8 %) and 148 (49.7 %) patients before and after chemotherapy, respectively. There was no correlation between the detection of CK-19mRNA+ CTCs after chemotherapy and the various known clinicopathologic parameters except with HER2 status. The incidence of detection of CK-19mRNA+ CTCs was significantly decreased after the administration of 3 (47.8 %; p < 0.001) or 6 (44.3 %; p = 0.001) chemotherapy cycles. The persistent detection of >2.25 CK-19mRNA+ CTCs both before and after chemotherapy (persistently high group) was associated with a significantly (p = 0.003) decreased overall survival. In addition, chemotherapy-induced decrease of CK-19mRNA+ CTCs (≤2.25 CTCs) was associated with a better survival (47 vs 34 months; p < 0.001). Failure of chemotherapy to decrease the CK-19mRNA+ CTCs ≤2.25 was associated with decreased overall survival (HR 1.405, 95 % CI 1.044-1.891; p = 0.025) whereas in multivariate analysis the persistence of >2.25 CTCs both before and after chemotherapy was emerged as an independent prognostic factor (HR 1.661, 95 % CI 1.070-2.579; p = 0.024).

Conclusion: Detection of CK-19mRNA+ CTCs after the completion of front-line chemotherapy in patients with MBC is associated with poor survival and may be a useful tool for the evaluation of front-line chemotherapy.