Systemic Therapy for Metastatic Triple Negative Breast Cancer: Current Treatments and Future Directions

Until recently, despite its heterogenous biology, metastatic triple negative breast cancer (TNBC) was treated as a single entity, with successive lines of palliative chemotherapy being the only systemic option. Significant gene expression studies have demonstrated diversity TNBC, but effective differential targeting four main (Basal-like 1 and 2, mesenchymal luminal androgen receptor) molecular sub-types has largely eluded researchers. The introduction immunotherapy, currently useful for patients PD-L1 positive cancers, led to stratification first-line therapy using this immunohistochemical biomarker. Germline BRCA mutations can also be targeted PARP inhibitors in both adjuvant settings. In contrast, benefit anti-Trop-2 antibody-drug conjugate (ADC) Sacituzumab govitecan (SG) does not appear confined tumours expressing high levels Trop-2, leading potential utility any patient an estrogen receptor (ER)-negative, HER2-negative advanced (ABC). Most low HER2 expression, detected up 60% predicts from potent HER2-directed trastuzumab deruxtecan (T-DXd), defining additional treatment option sub-group. Regrettably, recent advances, median survival TNBC continues lag far behind approximately 5 years now expected ER-positive or HER2-positive cancers. We review data supporting ADCs, agents subgroups current clinical trials that may pave way further advances challenging disease.