title: Cytokeratin-19 mRNA-positive circulating tumor cells during follow-up of patients with operable breast cancer: prognostic relevance for late relapse.
abstract: BACKGROUND
  The detection of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTC) before and/or after adjuvant chemotherapy in patients with operable breast cancer is associated with poor clinical outcome. Reliable prognostic markers for late disease relapse are not available. In this study we investigated the value of CTC detection during the first five years of follow-up in predicting late disease relapse.
  
  
  METHODS
  Blood was analyzed from 312 women with operable breast cancer who had not experienced disease relapse during the first two years of follow-up. A real-time reverse transcriptase polymerase chain reaction (RT-PCR) for CK-19 mRNA was used to detect CTC three months after the completion of adjuvant chemotherapy and every six months thereafter for a follow-up period of five years.
  
  
  RESULTS
  Eighty patients (25.6% of the study population) remained CTC free throughout the five-year period. A change in CTC status was observed in 133 patients (42.6%); 64 patients (20.5%) with initially CK-19 mRNA-positive CTC during the first 24 months turned CTC-negative afterwards while 69 (22.1%) who were initially CTC-negative became CTC-positive. Ninety-nine patients (31.7%) remained persistently CK-19 mRNA-positive. After a median follow-up period of 107 months (range: 38 to 161 months), the persistently CTC-positive patients with either hormonal receptor positive or negative tumors, had a higher risk of late-disease relapse compared to the persistently CTC-negative patients (36.4% versus 11.2%, P <0.001). Multivariate analysis revealed that persistently CTC-positive patients also had a shorter disease-free (P = 0.001) and overall survival (P = 0.001).
  
  
  CONCLUSIONS
  Persistent detection of CK-19 mRNA-positive CTC during the first five years of follow-up is associated with an increased risk of late relapse and death in patients with operable breast cancer and indicates the presence of chemo-and hormonotherapy-resistant residual disease. This prognostic evaluation may be useful when deciding on subsequent adjuvant systemic therapy.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Saloustros
authors.forename: Maria
authors.initials: M
authors.lastname: Perraki
authors.forename: Stella
authors.initials: S
authors.lastname: Apostolaki
authors.forename: Galatea
authors.initials: G
authors.lastname: Kallergi
authors.forename: Alexandros
authors.initials: A
authors.lastname: Xyrafas
authors.forename: Kostas
authors.initials: K
authors.lastname: Kalbakis
authors.forename: Sophia
authors.initials: S
authors.lastname: Agelaki
authors.forename: Antonia
authors.initials: A
authors.lastname: Kalykaki
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053539:Keratin-19 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D012333:RNA, Messenger