The evolution of knowledge of triple-negative breast cancer: from biology to novel drug treatment

Triple-negative breast cancer (TNBC) is definied by the lack of expression of the estrogen receptor, progesterone receptor and HER2. TNBC has been characterized by aggressive course, early development of metastases, poor overall survival rates compared to other subtypes of breast cancer. Molecular genetic studies have allowed to discover different molecular subtypes of TNBC (i.e., basal-like, claudin-low), demonstrated the presence of «immune-activated» subtypes with better disease outcome. In addition, further studies have characterized molecular features characteristic of TNBC, including a high rates of TP53 mutations, MEK and PI3K pathway activation, loss RB1 protein function, genetic similarities to serous ovarian cancers, including inactivation of BRCA pathway. Understanding of the genetic heterogeneity of TNBC led to promising therapeutic approaches, including DNA-damaging agents (i.e., platinum salts and PARP inhibitors) and immunotherapy currently. Platinum salts became a standard component in the chemotherapy regimens for patients with metastatic TNBC. The best outcomes are observed among patients with BRCA-mutation. Furthermore, the use of platinum salts in neoadjuvant regimens showes higher pathologic complete response rates. The presence of tumor infiltrating lymphocytes in TNBC carries prognostic role. The use of checkpoint inhibitors, including PD-1 and PD-L1 inhibitors, actively investigated in the setting of metastatic TNBC. For oncologists it's very important to have ability to assign the optimal therapeutics regimens, based on knowledge of the heterogeneity of TNBC, that would led to improve patient outcome.