Published in:

Open Access 26-05-2024 | Breast Cancer | Research

The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

Authors: Emma Rewcastle, Ivar Skaland, Einar Gudlaugsson, Silja Kavlie Fykse, Jan P. A. Baak, Emiel A. M. Janssen

Published in: Breast Cancer Research and Treatment | Issue 1/2024

Abstract

Purpose

Quantification of Ki67 in breast cancer is a well-established prognostic and predictive marker, but inter-laboratory variability has hampered its clinical usefulness. This study compares the prognostic value and reproducibility of Ki67 scoring using four automated, digital image analysis (DIA) methods and two manual methods.

Methods

The study cohort consisted of 367 patients diagnosed between 1990 and 2004, with hormone receptor positive, HER2 negative, lymph node negative breast cancer. Manual scoring of Ki67 was performed using predefined criteria. DIA Ki67 scoring was performed using QuPath and Visiopharm® platforms. Reproducibility was assessed by the intraclass correlation coefficient (ICC). ROC curve survival analysis identified optimal cutoff values in addition to recommendations by the International Ki67 Working Group and Norwegian Guidelines. Kaplan–Meier curves, log-rank test and Cox regression analysis assessed the association between Ki67 scoring and distant metastasis (DM) free survival.

Results

The manual hotspot and global scoring methods showed good agreement when compared to their counterpart DIA methods (ICC > 0.780), and good to excellent agreement between different DIA hotspot scoring platforms (ICC 0.781–0.906). Different Ki67 cutoffs demonstrate significant DM-free survival (p < 0.05). DIA scoring had greater prognostic value for DM-free survival using a 14% cutoff (HR 3.054–4.077) than manual scoring (HR 2.012–2.056). The use of a single cutoff for all scoring methods affected the distribution of prediction outcomes (e.g. false positives and negatives).

Conclusion

This study demonstrates that DIA scoring of Ki67 is superior to manual methods, but further study is required to standardize automated, DIA scoring and definition of a clinical cut-off.

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Title: The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer
Authors: Emma Rewcastle
Ivar Skaland
Einar Gudlaugsson
Silja Kavlie Fykse
Jan P. A. Baak
Emiel A. M. Janssen
Publication date: 26-05-2024
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Artificial Intelligence
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 1/2024
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-024-07352-4

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The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

Abstract

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Results

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