The evolving management of metastatic triple negative breast cancer

Advanced triple negative breast cancer (TNBC) is an incurable disease classified by its lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. Due to its lack of therapeutic targets, it has historically been treated with single agent chemotherapy, with combination cytotoxic therapy typically reserved for patients with high disease burdens, symptomatic disease, and/or impending visceral crisis. Recent molecular analyses have revealed that this clinical group of TNBCs is in fact quite biologically heterogeneous, with multiple TNBC subtypes defined by distinct biology and clinical behavior. Building on this biology, 2 targeted strategies are now approved for selected patients with advanced TNBC: the poly (ADP-ribose) polymerase inhibitors for advanced TNBC with a germline mutation in BRCA1/2, and the combination of the programmed death ligand 1-specific antibody atezolizumab with nab-paclitaxel for advanced TNBC that expresses programmed death ligand 1 on immune cells within the tumor. These targeted agents tend to be associated with a more favorable side effect profile and longer disease control than standard chemotherapy. A number of other targeted therapies have shown promise in early clinical trials, and several are now in definitive phase 3 testing for advanced TNBC. These include the antiapoptotic kinase inhibitors ipatisertib and capivasertib, and the antibody-drug conjugate sacituzumab govitecan-hziy. Approved biomarker-driven treatment options for this disease are thus likely to expand in the near-term. Here we review current treatment options and emerging targeted therapies for advanced TNBC. For patients who do not meet criteria for approved targeted therapies, participation in clinical trials evaluating precision medicines with candidate predictive biomarkers in advanced TNBC should be encouraged.