title: Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer.
abstract: OBJECTIVE
  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).
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, P.O. Box 1352, Voutes, 71110, Heraklion, Crete, Greece, georgoul@med.uoc.gr.
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: S
authors.initials: S
authors.lastname: Apostolaki
authors.forename: V
authors.initials: V
authors.lastname: Bozionelou
authors.forename: E
authors.initials: E
authors.lastname: Politaki
authors.forename: M
authors.initials: M
authors.lastname: Perraki
authors.forename: N
authors.initials: N
authors.lastname: Georgoulia
authors.forename: K
authors.initials: K
authors.lastname: Kalbakis
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.forename: A
authors.initials: A
authors.lastname: Xyrafas
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D053539:Keratin-19; D012333:RNA, Messenger