title: Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status.
abstract: BACKGROUND
  To evaluate the incidence of central nervous system (CNS) involvement in patients with breast cancer treated with a taxane-based chemotherapy regimen and to determine predictive factors for CNS relapse.
  
  
  METHODS
  The medical files of patients with early breast cancer (n = 253) or advanced stage breast cancer (n = 239) as well of those with other solid tumors (n = 336) treated with or without a taxane-based chemotherapy regimen during a 42-month period were reviewed. HER2/neu overexpression was identified by immunohistochemistry, whereas cytokeratin 19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in the peripheral blood were identified by real-time PCR.
  
  
  RESULTS
  The incidence of CNS relapse was similar in patients suffering from breast cancer or other solid tumors (10.4% and 11.4%, respectively; P = 0.517). The incidence of CNS relapse was significantly higher in breast cancer patients with advanced disease (P = 0.041), visceral disease and bone disease (P = 0.036), in those who were treated with a taxane-containing regimen (P = 0.024), in those with HER2/neu-overexpressing tumors (P = 0.022) and, finally, in those with detectable CK-19 mRNA-positive CTCs (P = 0.008). Multivariate analysis revealed that the stage of disease (odds ratio, 0.23; 95% confidence interval, 0.007-0.23; P = 0.0001), the HER2/neu status (odds ratio, 29.4; 95% confidence interval, 7.51-101.21; P = 0.0001) and the presence of CK-19 mRNA-positive CTCs (odds ratio, 8.31; 95% confidence interval, 3.97-12.84; P = 0.001) were independent predictive factors for CNS relapse.
  
  
  CONCLUSIONS
  CNS relapses are common among breast cancer patients treated with a taxane-based chemotherapy regimen, patients with HER2/neu-positive tumor and patients with CK-19 mRNA-positive CTCs.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece. georgsec@med.uoc.gr
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
authors.forename: Lambros
authors.initials: L
authors.lastname: Vamvakas
authors.forename: Stella
authors.initials: S
authors.lastname: Apostolaki
authors.forename: Maria
authors.initials: M
authors.lastname: Perraki
authors.forename: Zacharenia
authors.initials: Z
authors.lastname: Saridaki
authors.forename: Irine
authors.initials: I
authors.lastname: Kazakou
authors.forename: Athanasios
authors.initials: A
authors.lastname: Pallis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kouroussis
authors.forename: Nikos
authors.initials: N
authors.lastname: Androulakis
authors.forename: Kostas
authors.initials: K
authors.lastname: Kalbakis
authors.forename: Georgia
authors.initials: G
authors.lastname: Millaki
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
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* / Q000503:physiopathology*; D016543:Central Nervous System Neoplasms / Q000503:physiopathology* / Q000556:secondary; D005260:Female; D006801:Humans; D053539:Keratin-19; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011237:Predictive Value of Tests; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D043823:Taxoids / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D053539:Keratin-19; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids