Global scoring method of Ki67 immunohistochemistry in breast cancer demonstrates improved concordance using real-world multi-institutional data.

Ki67 is a broadly available biomarker of proliferation with various approaches to its evaluation in breast cancer. The International Ki67 in Breast Cancer Working Group (IKWG) recommends calculating Ki67 globally across the tumor area, as this method offers high interobserver concordance. These recommendations have been integrated into many international breast cancer guidelines (ASCO, ESMO), yet there is no real-world data on if it improved inter-pathologists and inter-laboratory variability. Here, we present the first real-world data on the variability and impact of Ki67 scores on clinical decision-making in breast cancer when using hotspot scoring and after implementing IKWG global scoring method in clinical practice. We extracted hotspot and global scoring results from 4313 breast cancer patients from routine diagnostics, categorizing the scores into three clinical risk groups over a one-year period across two large breast centers in Stockholm, Sweden. Variability between pathologists was not clinically significant. The global scoring method improved inter-laboratory consistency but also led to a notable increase in cases classified as intermediate at both centers This has been captured in the 2022 Swedish clinical breast cancer guidelines recommending molecular profiling test for patients with Grade II, global Ki67 intermediate score, T1c / T2 breast cancer. To conclude, our findings demonstrate acceptable consistency in Ki67 scores among individual pathologists across both scoring methods, however high inter-laboratory variability was observed with hot spot scoring. Global Ki67 scoring demonstrated low inter-laboratory variability in real world breast cancer care, thereby increasing the reliability of Ki67 assessment in clinical decision-making.