title: Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.
abstract: OBJECTIVE
  To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer.
  
  
  METHODS
  Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%.
  
  
  RESULTS
  Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09).
  
  
  CONCLUSIONS
  Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.
authors.affiliation: Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy. giuseppe.viale@ieo.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Mauro G
authors.initials: MG
authors.lastname: Mastropasqua
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dell'Orto
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.forename: Gaëtan
authors.initials: G
authors.lastname: MacGrogan
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Braye
authors.forename: Christian
authors.initials: C
authors.lastname: Ohlschlegel
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Orosz
authors.forename: Wojciech P
authors.initials: WP
authors.lastname: Olszewski
authors.forename: Fiona
authors.initials: F
authors.lastname: Knox
authors.forename: Beat
authors.initials: B
authors.lastname: Thürlimann
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Barry A
authors.initials: BA
authors.lastname: Gusterson
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D004703:Endocrine System; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole