UK recommendations for Ki-67 immunohistochemical staining and interpretation in breast cancer

Ki-67 is a well-established marker of tumour proliferation and an important prognostic and predictive biomarker in breast cancer, particularly in hormone receptor-positive (HR-positive), HER2-negative disease. Despite its biological relevance, clinical implementation has been limited by the reported interobserver and interlaboratory variability. Recent therapeutic advances have created an increased need for accurate and reproducible Ki-67 assessment in clinical practice. This review summarizes the biological basis for the use of Ki-67 as a marker of proliferation, technical requirements for reliable immunohistochemistry and the influence of pre-analytical and analytical variables on staining performance. We evaluate established and emerging scoring approaches and provide scoring recommendations for practising pathologists. A simplified calibrated global assessment method is presented as an alternative to exhaustive visual quantification that preserves its accuracy while substantially reducing scoring time and avoiding the variability of estimated methods. Image analysis/artificial intelligence (AI) using validated algorithms is recommended where available. We also review the role of Ki-67 in predicting response to neoadjuvant endocrine and chemotherapy, its integration into prognostic models such as the PEPI score, and its utility in selecting patients for adjuvant CDK4/6 inhibition. The limitations of fixed cut-off values are discussed, together with the potential advantages of tiered classification and continuous modelling. Finally, we outline the growing role of digital pathology and AI, which have demonstrated improved reproducibility, reduced turnaround time, and prognostic performance superior to manual scoring. Ki-67 is a clinically meaningful biomarker, the value of which can only be fully realized through rigorous standardization, validated scoring approaches and close communication between pathologists and oncologists. This guidance provides a practical framework for high-quality Ki-67 assessment and supports its safe and effective integration into contemporary breast cancer management.