Prognostic Significance and Molecular Classification of Triple Negative Breast Cancer: A Systematic Review

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Despite accounting for 15-20% of all breast cancer cases, TNBC is associated with poor prognosis and a high likelihood of recurrence and metastasis. Understanding the molecular subtypes of TNBC is important for developing targeted therapies and improving patient outcomes. This systematic review aimed to assess the prognostic significance of molecular subtypes of TNBC and the implications for therapeutic management. A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify studies focusing on the molecular classification of TNBC and its prognostic relevance. Studies were included based on specific inclusion criteria, including original research evaluating clinical outcomes and survival data in molecularly classified TNBC cohorts. Data were extracted, synthesized, and analyzed to determine the prognostic implications of different TNBC subtypes. The review identified several distinct molecular subtypes of TNBC, including basal-like, mesenchymal, immune-modulatory, and luminal androgen receptor (LAR) subtypes. Basal-like TNBC was associated with poor prognosis and high rates of recurrence, while immune-modulatory TNBC exhibited better survival outcomes, particularly in patients with high levels of tumor-infiltrating lymphocytes. Mesenchymal and LAR subtypes exhibited diverse clinical behavior and varying therapeutic responses. Furthermore, key prognostic biomarkers, such as BRCA1/2 mutations and programmed death-ligand 1 expression, were highlighted which have therapeutic implications. Molecular classification of TNBC provides valuable prognostic information and guides therapeutic strategies. Integrating molecular subtyping into clinical decision-making will be essential for the development of personalized treatments and improved outcomes for TNBC patients. However, further research is needed to refine classification systems and address existing therapeutic gaps in TNBC management.