title: Long-term prognostic performance of Ki67 rate in early stage, pT1-pT2, pN0, invasive breast carcinoma.
abstract: BACKGROUND
  Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1-pT2, pN0) breast cancer patients.
  
  
  METHODS
  456 patients treated in 1995-1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed.
  
  
  RESULTS
  All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5-191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8-4.8), p<10e-06] and HG3 [HR = 4.4 (2.2-8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5-4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01-4.8), p = 0.04].
  
  
  CONCLUSIONS
  We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1-pT2, pN0, breast cancers.
authors.affiliation: Department of Surgery, Institut Curie, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.forename: David
authors.initials: D
authors.lastname: Hajage
authors.forename: Alexia
authors.initials: A
authors.lastname: Savignoni
authors.forename: Jean-Guillaume
authors.initials: JG
authors.lastname: Feron
authors.forename: Marc Andrew
authors.initials: MA
authors.lastname: Bollet
authors.forename: Youlia
authors.initials: Y
authors.lastname: Kirova
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Veronique
authors.initials: V
authors.lastname: Dieras
authors.forename: Virginie
authors.initials: V
authors.lastname: Fourchotte
authors.forename: Fatima
authors.initials: F
authors.lastname: Laki
authors.forename: Severine
authors.initials: S
authors.lastname: Alran
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D008940:Mitotic Index; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human