Abstract

Breast cancer is the most diagnosed cancer among women worldwide and represents a major global health burden due to its biological heterogeneity and variable clinical outcomes. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Molecularly heterogeneous and lacking targeted treatments, TNBC is associated with poor outcomes and high recurrence. This review evaluates the potential of CHEK1, TOP2A, and c-MET as biomarkers for companion diagnostics in TNBC. CHEK1 promotes DNA damage response and cell-cycle checkpoints, especially in p53-deficient tumours, and could serve as a predictive biomarker of sensitivity to CHEK1 inhibitors. TOP2A, which is involved in DNA replication and chromosomal segregation, is frequently overexpressed in highly proliferative TNBC and correlates with response to anthracycline-based chemotherapy. c-MET, a receptor tyrosine kinase, drives tumour progression, invasion, and therapeutic resistance; its overexpression is associated with poor clinical outcomes and has been linked to emerging targeted therapies. Collectively, CHEK1, TOP2A, and c-MET represent promising biomarkers for Companion diagnostic development in TNBC. However, further analytical validation, prospective clinical validation, and assay standardization efforts are needed prior to clinical use.

Key words: Breast cancer, Companion diagnostics, CHEK1, c-MET, TOP2A