Keratin as a Potential Prognostic Biomarker for Breast Cancer Progression: An Evidence-Synthesizing Narrative Review

Breast cancer (BC) remains a leading cause of mortality among females worldwide, making reliable biomarkers necessary for prognosis and personalized treatment. Keratins represent the largest and most diverse intermediate filament (IF) class utilized as marker proteins histopathologically because of their specific expression patterns related to epithelial differentiation. This narrative review explores the potential of keratin subtypes, which are extensively employed in the differentiation of specific BC subclasses, as prognostic markers.

This narrative review used a structured literature search in PubMed and Scopus. Selected elements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework were adapted to improve transparency in the search and screening process. A total of 79 were included, covering eleven in vitro, six in vivo, and 62 human studies.

The key findings highlight five significant keratin types: keratin 5/6 (K5/6), keratin 19 (K19), keratin 8/18 (K8/18), keratin 14 (K14), and keratin 17 (K17). These are expressed in specific BC subtypes and influence tumor progression through particular pathways. These keratin subtypes were selected for discussion as they are the most prevalent and clinically important keratins in BC and represent the strongest evidence base. In addition to their role in prognostic stratification, available evidence suggests that subtypes of keratin may serve to recognize metastatic potential early, influence adjuvant therapy decisions in high-risk subgroups, and monitor treatment responses dynamically. They serve as predictive biomarkers that help understand chemotherapy effectiveness, increase risk assessment in aggressive subsets of triple negative breast cancer (TNBC), and facilitate targeted therapeutic strategies, including K1-targeted peptide-doxorubicin conjugates demonstrating the potential for these factors to transition from merely predictive indicators to meaningful prognostic markers.

This review confirms that keratin actively contributes to tumor progression and emphasizes the importance of keratins in key oncogenic pathways, providing insights for the development of updated therapies.