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

Giuseppe Viale, Anita Giobbie-Hurder, Meredith M. Regan, Alan S. Coates, Mauro G. Mastropasqua, Patrizia Dell'Orto, Eugenio Maiorano, Gaëtan MacGrogan, Stephen G. Braye, Christian Öhlschlegel, Patrick Neven, Zsolt Orosz, Wojciech P. Olszewski, Fiona Knox, Beat Thürlimann, Karen N. Price, Monica Castiglione-Gertsch, Richard D. Gelber, Barry A. Gusterson, Aron Goldhirsch

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)5569-5575
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number34
DOIs
Publication statusPublished - Dec 1 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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