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. 2021 Jul 1;113(7):808-819.
doi: 10.1093/jnci/djaa201.

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

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

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

Torsten O Nielsen et al. J Natl Cancer Inst. .

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.

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Figures

Figure 1.
Figure 1.
The series of International Ki67 Working Group (IKWG) studies to standardize methods for visual scoring of Ki67 index in breast cancer. Intraclass correlation coefficient (ICC) through the 3 study phases (1, 2, 3 A visual and automated [3AI], 3B visual and automated [3AI-2]) are shown with error bars representing the lower and upper 95% credible intervals. The numeric values of the various ICCs are shown at the x-axis labels with the 95% credible intervals in parentheses. The horizontal bar lines represent observed ICCs. The extent of the vertical lines indicates 95% credible interval. The dotted grey color line indicates ICC = 0.8. TMA = tissue microarray.
Figure 2.
Figure 2.
Conclusions regarding the questions for Ki67 in breast cancer. ET = endocrine therapy; CTX = chemotherapy; ASCO = American Society of Clinical Oncology.
See this image and copyright information in PMC

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