title: Detection of circulating cytokeratin-19 mRNA-positive cells in the blood and the mitotic index of the primary tumor have independent prognostic value in early breast cancer.
abstract: BACKGROUND
  Previous studies showed that molecular detection of CK-19 mRNA in peripheral blood and the mitotic index of primary tumors have prognostic value in early breast cancer. The aim of this study was to assess the association between these variables.
  
  
  METHODS
  The primary tumors of 223 operable breast cancer patients (92 premenopausal and 131 postmenopausal) were evaluated for the MAI classified as either ≤ 5 per 10, 6 to 10 per 10 and > 10 per 10 or < 10 per 10 and ≥ 10 per 10 mitoses per high power field using a standardized protocol previously reported. Peripheral blood was also collected before and after the end of adjuvant chemotherapy for detection of CK-19 mRNA-positive cells using reverse transcription polymerase chain reaction previously described.
  
  
  RESULTS
  After a median follow-up of 118 months, 75 patients (33.6%) experienced disease relapse and 56 (25.1%) died of breast cancer. MAI was strongly associated with disease-free survival (DFS) and overall survival (OS) (P < .001 for DFS and OS together). Detecting CK-19 mRNA-positive cells in the peripheral blood before but not after adjuvant chemotherapy was associated with marginally worse DFS (P = .055) and OS (P = .059). Cox regression analysis revealed that MAI and CK-19 mRNA-positive cell detection before adjuvant chemotherapy were independent variables associated with decreased DFS (P < .001 and P = .038, respectively) and OS (P < .001 and P = .029, respectively). There was no significant interaction between MAI and detection of CK-19 mRNA-positive cells.
  
  
  CONCLUSIONS
  MAI of the primary tumor and detection of CK-19 mRNA-positive cells in the blood before adjuvant chemotherapy in early breast cancer patients are 2 independent prognostic factors associated with clinical outcome.
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
authors: Konstantinos
authors: K
authors: Tryfonidis
authors: Department of Pathology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
authors: Maria
authors: M
authors: Kafousi
authors: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: Maria
authors: M
authors: Perraki
authors: Department of Pathology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
authors: Stella
authors: S
authors: Apostolaki
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: Sofia
authors: S
authors: Agelaki
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors: Vassilis
authors: V
authors: Georgoulias
authors: Department of Pathology, University General Hospital of Heraklion, Heraklion, Crete, Greece.
authors: Efstathios
authors: E
authors: Stathopoulos
authors: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece. Electronic address: mavrudis@med.uoc.gr.
authors: Dimitris
authors: D
authors: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053539:Keratin-19 / Q000235:genetics*; D008875:Middle Aged; D008940:Mitotic Index; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D012333:RNA, Messenger
keywords: Adjuvant chemotherapy; Circulating tumor cells; Early breast cancer; Mitotic activity index; Prognosis