Evaluation of the international Ki67 working group cut point recommendations for early breast cancer: comparison with 21-gene assay results in a large integrated health care system
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Published:2023-10-17
Issue:2
Volume:203
Page:281-289
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ISSN:0167-6806
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Container-title:Breast Cancer Research and Treatment
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language:en
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Short-container-title:Breast Cancer Res Treat
Author:
Shim Veronica C., Baker Robin J., Jing Wen, Puentes Roisin, Agersborg Sally S., Lee Thomas K., GoreaI Wamda, Achacoso Ninah, Lee Catherine, Villasenor Marvella, Lin Amy, Kapali Malathy, Habel Laurel A.ORCID
Abstract
Abstract
Purpose
The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2−, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay.
Methods
We included 307 women aged 50+ years with node-negative, ER+PR+HER2− breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics.
Results
Depending on reader, 8.8–16.0% of our cohort had Ki67 ≤ 5% and 11.4–22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78–0.85); it was 0.79 (95% CI 0.74–0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71–0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively.
Conclusion
The IKWG’s Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.
Funder
The Permanente Medical Group (TPMG) Delivery Science Program
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
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