title: Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.
abstract: Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.
authors: INSERM, Centre d'Investigations Cliniques-9501, CHU Nancy & Nancy-Université, 54511 Vandoeuvre-les-Nancy, France. e.luporsi@nancy.unicancer.fr
authors: Elisabeth
authors: E
authors: Luporsi
authors: Fabrice
authors: F
authors: André
authors: Frédérique
authors: F
authors: Spyratos
authors: Pierre-Marie
authors: PM
authors: Martin
authors: Jocelyne
authors: J
authors: Jacquemier
authors: Frédérique
authors: F
authors: Penault-Llorca
authors: Nicole
authors: N
authors: Tubiana-Mathieu
authors: Brigitte
authors: B
authors: Sigal-Zafrani
authors: Laurent
authors: L
authors: Arnould
authors: Anne
authors: A
authors: Gompel
authors: Caroline
authors: C
authors: Egele
authors: Bruno
authors: B
authors: Poulet
authors: Krishna B
authors: KB
authors: Clough
authors: Hubert
authors: H
authors: Crouet
authors: Alain
authors: A
authors: Fourquet
authors: Jean-Pierre
authors: JP
authors: Lefranc
authors: Carole
authors: C
authors: Mathelin
authors: Nicolas
authors: N
authors: Rouyer
authors: Daniel
authors: D
authors: Serin
authors: Marc
authors: M
authors: Spielmann
authors: Margaret
authors: M
authors: Haugh
authors: Marie-Pierre
authors: MP
authors: Chenard
authors: Etienne
authors: E
authors: Brain
authors: Patricia
authors: P
authors: de Cremoux
authors: Jean-Pierre
authors: JP
authors: Bellocq
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen