[Recent therapeutic trends in triple-negative metastatic breast cancers: PARP inhibitors, immunotherapies and antibody-drug conjugates].

Compared with other breast cancer subtypes, patients with metastatic triple-negative breast cancer (TNBC) are younger and have a worst overall survival with a median of 15 to 18 months. These tumors have long suffered from a purely negative definition, but the last few years have witnessed many breakthrough genomic and molecular findings, that could dramatically improve our understanding of the biological heterogeneity of TNBC. Moreover, based on these genomic analyses, new generation of clinical trials, using many innovative therapies directed against novel targets, had been conducted. Some TNBC have DNA damage response defects, particularly linked to germinal BRCA1/2 mutations. At the present time, two poly(ADP-ribose) polymerase (PARP) inhibitors have been approved for patients with germinal BRCA1/2 mutation. Breast cancers are not the more immunogenic solid tumors, but some of them have a high percentage of tumor infiltrating lymphocytes (TILs), express PD-L1 (about 40%) or have a high tumor mutational burden. These features of TNBC have given a strong rational to investigate the role of immune checkpoint inhibitors. One of them has been approved by FDA in association with a cytotoxic as a first line treatment. At last, targeting surface receptors outside genomic landscape with antibody drug conjugate (ADC) is a new strategy for metastatic TNBC. Sacituzumab-govitecan is the first ADC approved by FDA in advanced TNBC beyond two lines of treatment.