Management of Metastatic Triple-negative Breast Cancer: Focus on Targeted Therapies

Triple-negative breast cancer (TNBC) is a heterogeneous disease that is historically difficult to treat, but advances in molecular targeted therapies, including the use of antibodies, are changing the standard of care. Translational research over the years has revealed various actionable targets allowing TNBC to be subtyped in novel ways. In this article, we review the molecular targets that guide current management of patients with metastatic TNBC (mTNBC), including programmed death-ligand 1, germline BRCA1 and BRCA2 mutations, and the transmembrane glycoprotein Trop-2. These targets allow for the treatment of mTNBC with immunotherapy, poly(ADP-ribose)polymerase inhibitors, and antibody–drug conjugates (ADC), such as sacituzumab govitecan, the first ADC approved for the treatment of breast cancer. We also review upcoming therapies, such as datopotamab deruxtecan and trastuzumab deruxtecan. Although mTNBC is complex in nature, molecular studies are making treatments more personalized by identifying actionable targets in what was once thought to be a non-targetable disease.