Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous clinical breast cancer subtype that currently lacks approved targeted therapies. Research aimed at understanding the mutational and transcriptional landscape of TNBC is being achieved through gene expression analysis and large-scale genomic projects, resulting in identification of potential drug targets.
Design: A review of PubMed and conference databases was carried out to identify randomized clinical trials in TNBC as well as early phase trials of emerging targeted therapies.
Results and Discussion: The role of platinums and poly(ADP-ribose) polymerase inhibitors continues to be a focus of clinical trials with attention now on developing a predictive biomarker that identifies “BRCA-like” tumours. The previously identified six TNBC subtypes has been revised to four and has provided further insight into the role of the androgen receptor and immune system, both of which are emerging as promising targets in select patients either as monotherapy or in combination with other immune therapies, chemotherapy or targeted therapy. Other novel targets include MET inhibition and signaling pathways such as the MAPK, PI3K and JAK/STAT pathways. Antibody-drug conjugates are also of interest. Targeting the angiogenesis and epidermal growth factor receptor pathways have had limited efficacy in the treatment of TNBC.
Conclusions: As researchers begin to understand the underlying biology of TNBC and identify predictive biomarkers, more select patient populations are being treated with targeted therapies, which is a promising step forward in filling the current void of approved targeted treatment options for patients with TNBC.
Key Words: androgen receptor, breast cancer, breast cancer molecular subtypes, cancer treatment, immune checkpoint blockade, targeted therapy, triple-negative breast cancer.