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

J Clin Oncol. 2008 Dec 1;26(34):5569-75. doi: 10.1200/JCO.2008.17.0829. Epub 2008 Nov 3.

Abstract

Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Endocrine System
  • Female
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Letrozole
  • Nitriles / therapeutic use*
  • Postmenopause
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Tamoxifen / therapeutic use*
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Ki-67 Antigen
  • Nitriles
  • Triazoles
  • Tamoxifen
  • Letrozole