Clinical Study

British Journal of Cancer (2007) 96, 1504–1513. doi:10.1038/sj.bjc.6603756 www.bjcancer.com
Published online 24 April 2007

Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients

This article was partially presented at the San Antonio Breast Cancer Symposium 2005.

E de Azambuja1,2, F Cardoso1, G de Castro Jr1, M Colozza3, M S Mano1, V Durbecq1, C Sotiriou1, D Larsimont1, M J Piccart-Gebhart1 and M Paesmans4

  1. 1Medical Oncology Clinic, Jules Bordet Institute, 125 Boulevard de Waterloo, 1000, Brussels, Belgium
  2. 2PhD student in the Programa de Pós-graduação em Medicina, Ciências Médicas, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, 2400 Ramiro Barcelos, 90035-003, Porto Alegre, Brazil
  3. 3SC Oncologia Medica, Azienda Ospedaliera, Via Brunamonti, 51-06122, Perugia, Italy
  4. 4Data Centre, Jules Bordet Institute, 125 Boulevard de Waterloo, 1000, Brussels, Belgium

Correspondence: M Paesmans, E-mail: marianne.paesmans@bordet.be

Received 18 January 2007; Revised 26 March 2007; Accepted 26 March 2007; Published online 24 April 2007.

Top

Abstract

The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR=1.93 (95% confidence interval (CI): 1.74–2.14); P<0.001), in node-negative patients (HR=2.31 (95% CI: 1.83–2.92); P<0.001) and in node-positive patients (HR=1.59 (95% CI: 1.35–1.87); P<0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR=1.95 (95% CI: 1.70–2.24; P<0.001)), node-negative patients (HR=2.54 (95% CI: 1.65–3.91); P<0.001) and node-positive patients (HR=2.33 (95% CI: 1.83–2.95); P<0.001). Our meta-analysis suggests that Ki-67/MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC.

Keywords:

breast cancer, Ki-67, prognostic value, meta-analysis