New Treatment Approaches for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) was first described as a distinct disease entity 20 years ago. Since that time, there has been tremendous effort invested in understanding the clinical features and biology of this breast cancer subtype and developing novel therapeutics specifically targeted for this group of tumors. This review will focus on therapeutic advances in the treatment of metastatic TNBC, outlining successes that contributed to expanded treatment options for advanced TNBC at present and highlight areas of ongoing investigation with potential to further advance treatment paradigms for this aggressive breast cancer subtype. Since 2018, five new therapies have been introduced into clinical practice for the treatment of advanced TNBC. Poly(ADP-ribose) polymerase inhibitors represent the only success for genomically targeted therapy, and this is an option only for a small subgroup of patients with TNBC and a germline BRCA1 or BRCA2 pathogenic variant. Pembrolizumab is currently the only PD-1 checkpoint inhibitor approved in the United States in combination with chemotherapy in the first-line setting and is an option for roughly 40% of patients with PD-L1 positive tumors. Antibody-drug conjugates have been an important advance in the treatment of advanced TNBC, although these drugs do not represent a TNBC-specific advance as both sacituzumab govitecan and trastuzumab deruxtecan have activity in breast tumors beyond TNBC. Thus, despite significant strides over the past decade, significant unmet clinical need persists, and novel therapeutics remain a pressing need for the treatment of advanced TNBC.