Innovations in targeted therapies for triple negative breast cancer

Abstract

Purpose of review: Triple negative breast cancer (TNBC) is defined by a lack of targets, namely hormone receptor (HR) expression and human epidermal growth factor receptor 2 amplification. Cytotoxic chemotherapy remains the mainstay of treatment. Though TNBC constitutes approximately 10-15% of breast cancer, it is disproportionally lethal, but it is hoped that outcomes will improve as targetable oncogenic drivers are identified.

Recent findings: Translational work in TNBC has focused on subsets defined by defects in homologous recombination repair, immune cell infiltration, or programmed death ligand receptor 1 expression, an over-active phosphoinositide-3 kinase pathway, or expression of androgen receptors. Though not specific to TNBC, the novel cell surface antigen trophoblast antigen 2 has also been identified and successfully targeted. This work has led to Food and Drug Administration approvals for small molecule poly-ADP-ribosyl polymerase inhibitors in patients with deleterious germline mutations in BRCA1 or BRCA2, the combination of nab-paclitaxel with immune checkpoint inhibitor antibodies in the first-line metastatic setting for programmed death ligand receptor 1+ TNBC, and use of the antibody-drug conjugate sacituzumab govitecan in the later-line metastatic setting.

Summary: Identification of targetable oncogenic drivers in TNBC is an area of intense cancer biology research, hopefully translating to new therapies and improved outcomes.

Trial registration: ClinicalTrials.gov NCT02574455 NCT03901339.