Triple-Negative Breast Cancer: Molecular Subtypes, Therapeutic Challenges, and Emerging Strategies—A Systematic Review

BACKGROUND Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, accounting for 15–20% of breast cancer cases. OBJECTIVE To review TNBC’s molecular heterogeneity, current therapies, and future directions. METHODS A literature search (2010–2025) was conducted using PubMed, Scopus, and Web of Science, focusing on clinical trials, molecular subtyping, and targeted therapies. RESULTS TNBC exhibits diverse molecular subtypes (basal-like, immunomodulatory, and luminal androgen receptor LAR) with distinct therapeutic responses. Chemotherapy (taxanes, anthracyclines, and platinum agents) remains the mainstay, while PARP inhibitors, immune checkpoint blockers (e.g., pembrolizumab), and androgen receptor antagonists show promise in subtype-specific contexts. Despite advances, resistance and poor prognosis persist, necessitating biomarker-driven strategies. CONCLUSION Personalized therapy based on molecular profiling and clinical trials targeting novel pathways (e.g., Wnt/β-catenin, NOTCH) is critical for improving TNBC outcomes.