Ki-67 Expression and Its Prognostic Significance in Breast Carcinoma: A Systematic Review

Abstract

Background: Breast carcinoma remains the most frequently diagnosed cancer among women worldwide and a major cause of cancer-related mortality. Ki-67, a nuclear proliferation marker expressed during active phases of the cell cycle, has become an important immunohistochemical biomarker used in breast cancer classification, prognostic assessment, and treatment decision-making. Objective: This systematic review aimed to evaluate the expression and prognostic significance of Ki-67 in breast carcinoma and its association with clinicopathological characteristics, molecular subtypes, and survival outcomes. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Electronic databases including PubMed, Scopus, Web of Science, ERIC, and Google Scholar were searched for studies evaluating Ki-67 expression in breast carcinoma using immunohistochemistry. Eligible studies included observational studies assessing associations between Ki-67 expression and prognostic or clinicopathological parameters. Data extraction and quality assessment were performed independently by two reviewers using the Newcastle-Ottawa Scale and Joanna Briggs Institute appraisal tools. Results: Twenty-four studies were included in the qualitative synthesis. Elevated Ki-67 expression consistently correlated with aggressive clinicopathological characteristics including higher histological grade, larger tumour size, lymph node involvement, HER2 overexpression, hormone receptor negativity, and triple-negative molecular subtype. High Ki-67 expression was also associated with poorer disease-free survival and overall survival. Several studies highlighted the role of Ki-67 in distinguishing luminal A from luminal B breast cancer subtypes and guiding therapeutic stratification. However, variability in scoring systems, cut-off values, and immunohistochemical protocols remained significant challenges. Conclusion: Ki-67 is a valuable proliferative and prognostic biomarker associated with aggressive tumour behaviour and adverse outcomes in breast carcinoma. Despite challenges related to standardisation and reproducibility, Ki-67 remains clinically useful in prognostic evaluation and treatment planning. Further large-scale studies using standardised methodologies are warranted, including population-specific investigations in settings where local evidence remains limited.