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.