Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review
Open Access
- 3 November 2011
- journal article
- review article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 132 (3), 895-915
- https://doi.org/10.1007/s10549-011-1837-z
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.Keywords
This publication has 117 references indexed in Scilit:
- Ki67 in breast cancer: prognostic and predictive potentialThe Lancet Oncology, 2010
- Reporting of prognostic studies of tumour markers: a review of published articles in relation to REMARK guidelinesBritish Journal of Cancer, 2009
- Aromatase expression and outcomes in the P024 neoadjuvant endocrine therapy trialBreast Cancer Research and Treatment, 2008
- NEAT: National Epirubicin Adjuvant Trial – toxicity, delivered dose intensity and quality of lifeBritish Journal of Cancer, 2008
- Letrozole in the neoadjuvant setting: the P024 trialBreast Cancer Research and Treatment, 2007
- Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patientsBritish Journal of Cancer, 2007
- Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozoleBritish Journal of Cancer, 2006
- Common markers of proliferationNature Reviews Cancer, 2006
- Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trialsThe Lancet, 2005
- The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67Breast Cancer Research and Treatment, 2000