Role of PCSK9 in breast cancer: a systematic review of its mechanistic pathways and clinical relevance

Abstract

Introduction Breast cancer is a heterogeneous disease in which accurate classification based on biomarker expression is essential for effective therapeutic decision-making. Consequently, the identification of novel biomarkers remains a research priority. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein (LDL) metabolism via its interaction with the LDL receptor (LDLR), has been extensively studied in cardiovascular disease. More recently, emerging evidence indicates that PCSK9 is highly expressed in several malignancies and may contribute to cancer progression, including in breast cancer. Methods A systematic literature review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines. PubMed (NCBI), Scopus, and Google Scholar were searched for studies published between 9 and 16 September 2025. Eligible studies included experimental (in vitro, in vivo, and in silico) and clinical investigations evaluating the role of PCSK9 in breast cancer. Given the heterogeneity in study designs and outcomes, findings were synthesized narratively. Results Nineteen studies met the inclusion criteria. Preclinical evidence consistently demonstrates that PCSK9 promotes tumorigenesis by enhancing cell proliferation, migration, invasion, and metastasis, supporting its potential as a biomarker and therapeutic target. However, clinical findings remain inconsistent, with conflicting evidence regarding the association between PCSK9 expression and patient prognosis. Conclusion In conclusion, while preclinical studies indicate a pro-tumorigenic role for PCSK9, its clinical significance in breast cancer appears to be context-dependent. The effects of PCSK9 vary according to molecular subtype and are influenced by the tumor microenvironment. Further well-designed studies are needed to clarify its prognostic value and potential as a target for personalized therapy.