Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Group

  • J Natl Cancer Inst. 2021 Jul 1;113(7):808-819. doi: 10.1093/jnci/djaa201.
Torsten O Nielsen  1 ,  Samuel C Y Leung  1 ,  David L Rimm  2 ,  Andrew Dodson  3 ,  Balazs Acs  4  5 ,  Sunil Badve  6 ,  Carsten Denkert  7 ,  Matthew J Ellis  8 ,  Susan Fineberg  9 ,  Margaret Flowers  10 ,  Hans H Kreipe  11 ,  Anne-Vibeke Laenkholm  12 ,  Hongchao Pan  13 ,  Frédérique M Penault-Llorca  14 ,  Mei-Yin Polley  15 ,  Roberto Salgado  16  17 ,  Ian E Smith  18 ,  Tomoharu Sugie  19 ,  John M S Bartlett  20  21 ,  Lisa M McShane  22 ,  Mitch Dowsett  23 ,  Daniel F Hayes  24
Affiliations
  • 1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
  • 2. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
  • 3. The UK National External Quality Assessment Scheme for Immunocytochemistry and In-Situ Hybridisation, London, UK.
  • 4. Department of Oncology and Pathology, Cancer Centre Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
  • 5. Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Stockholm, Sweden.
  • 6. Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA.
  • 7. Philipps University Marburg and University Hospital Marburg, Marburg, Germany.
  • 8. Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
  • 9. Montefiore Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA.
  • 10. Breast Cancer Research Foundation, New York, NY, USA.
  • 11. Medical School Hannover, Institute of Pathology, Hannover, Germany.
  • 12. Department of Surgical Pathology, Zealand University Hospital, Slagelse, Denmark.
  • 13. Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • 14. Department of Pathology, Centre Jean Perrin and Université d'Auvergne, Clermont-Ferrand, France.
  • 15. Department of Public Health Sciences, University of Chicago Biological Sciences, Chicago, IL, USA.
  • 16. Department of Pathology, GasthuisZusters Antwerpen / Hospital Network Antwerp (GZA-ZNA), Antwerp, Belgium.
  • 17. Division of Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • 18. Breast Unit, Royal Marsden Hospital, London, UK.
  • 19. Department of Surgery, Kansai Medical University, Shinmachi, Hirakata City, Osaka Prefecture, Japan.
  • 20. Diagnostic Development Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • 21. Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK.
  • 22. Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.
  • 23. Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London, UK.
  • 24. University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
PMID: 33369635 DOI: 10.1093/jnci/djaa201
Abstract

Ki67 immunohistochemistry (IHC), commonly used as a proliferation marker in breast Cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 in Breast Cancer Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 IHC analytical validity and clinical utility in breast Cancer, including the series of scoring studies the IKWG conducted on centrally stained tissues. Consensus observations and recommendations are: 1) as for Estrogen receptor and HER2 testing, preanalytical handling considerations are critical; 2) a standardized visual scoring method has been established and is recommended for adoption; 3) participation in and evaluation of quality assurance and quality control programs is recommended to maintain analytical validity; and 4) the IKWG accepted that Ki67 IHC as a prognostic marker in breast Cancer has clinical validity but concluded that clinical utility is evident only for prognosis estimation in anatomically favorable estrogen receptor-positive and HER2-negative patients to identify those who do not need Adjuvant chemotherapy. In this T1-2, N0-1 patient group, the IKWG consensus is that Ki67 5% or less, or 30% or more, can be used to estimate prognosis. In conclusion, analytical validity of Ki67 IHC can be reached with careful attention to preanalytical issues and calibrated standardized visual scoring. Currently, clinical utility of Ki67 IHC in breast Cancer care remains limited to prognosis assessment in stage I or II breast Cancer. Further development of automated scoring might help to overcome some current limitations.