title: Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer.
abstract: BACKGROUND
  The purpose of this study was to evaluate the effect of adjuvant treatment with tamoxifen on the CK-19 mRNA+ cells in patients with early-stage breast cancer.
  
  
  METHODS
  CK-19 mRNA+ cells were prospectively and longitudinally detected using a specific real-time PCR assay for CK-19 mRNA in 119 patients with estrogen and/or progesterone receptor-positive tumors during the period of tamoxifen administration.
  
  
  RESULTS
  Twenty-two (18.5%) patients had detectable CK-19 mRNA+ cells after the completion of adjuvant chemotherapy and in 15 (68.2%) of them adjuvant tamoxifen could not eliminate these cells (persistently positive). In 68 (57.1%) patients, no CK-19 mRNA+ cells could be detected throughout the follow-up period (persistently negative). Seven (46.7%) of the 15 persistently positive and six (8.8%) of the 68 persistently negative patients developed disease recurrence (P = 0.00026). Persistency of CK-19 mRNA+ cells was associated with a significantly lower median disease-free interval (P = 0.0001) and overall survival (P = 0.0005). Multivariate analysis revealed that the detection of CK-19 mRNA+ cells during the administration of tamoxifen was associated with an increased risk of relapse [hazard ratio (HR) = 22.318, P = 0.00006] and death (HR = 13.954, P < 0.00001).
  
  
  CONCLUSIONS
  The detection of CK-19 mRNA+ cells throughout the period of adjuvant tamoxifen treatment is an independent poor prognostic factor in patients with early breast cancer.
authors.affiliation: Department of Medical Oncology,University General Hospital of Heraklion, Crete, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Xenidis
authors.forename: V
authors.initials: V
authors.lastname: Markos
authors.forename: S
authors.initials: S
authors.lastname: Apostolaki
authors.forename: M
authors.initials: M
authors.lastname: Perraki
authors.forename: A
authors.initials: A
authors.lastname: Pallis
authors.forename: G
authors.initials: G
authors.lastname: Sfakiotaki
authors.forename: D
authors.initials: D
authors.lastname: Papadatos-Pastos
authors.forename: L
authors.initials: L
authors.lastname: Kalmanti
authors.forename: M
authors.initials: M
authors.lastname: Kafousi
authors.forename: E
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics*; D008137:Longitudinal Studies; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D004965:Estrogen Antagonists; D053539:Keratin-19; D012333:RNA, Messenger; D013629:Tamoxifen