Triple-Negative Breast Cancer: the Current Aspects of Pathogenesis and Therapies

Triple-negative breast cancer (TNBC) is known as one of the most aggressive forms of breast cancer (BC), exhibiting high rates of disease progression and poor prognosis due to the lack of clear therapeutic targets and rapid development of tumor resistance to certain chemotherapeutic regimens. TNBC is considered a highly heterogeneous form of BC and is defined by the lack of estrogen receptor (ER) and progesterone receptor (PR) expression, and human epidermal growth factor receptor 2 (HER2) overexpression, thereby rendering the tumors non-susceptible to the targeted treatments. In recent years, significant progress was achieved in understanding TNBC pathogenesis to find a novel target for drug development. Currently, the recommended first-line treatment for TNBC is combined chemotherapy exhibiting a broad spectrum of the adverse systemic effects, also giving a rise to frequent cases of multidrug resistance in patients in later stages. Apart from that, the only targeted treatments that have been approved so far are anti-PD-L1 and PARP inhibitors, which demonstrated the moderate benefits only in the selected TNBC patient groups. Thus, discovering new targets and development of novel drugs for TNBC treatment is of the utmost need. The review focuses on the diverse molecular mechanisms of TNBC pathogenesis, including P53 mutations, RB1 loss, altered signaling pathways, etc. The review also describes the current aspects of diagnostic approaches, molecular and histological classifications, and current treatment recommendations. The molecular mechanisms underlying TNBC resistance to chemotherapy are also discussed. Lastly, the attractive druggable targets for TNBC therapy are also described. This is also supported by the ongoing phases I/II of the clinical trials for TNBC patients.