Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors

Abstract

The development of immunotherapy agents has revolutionized the field of oncology. The only FDA-approved immunotherapeutic approach in breast cancer consists of immune checkpoint inhibitors, yet several novel immune-modulatory strategies are being actively studied and appear promising. Innovative immunotherapeutic strategies are urgently needed in triple negative breast cancer (TNBC), a subtype of breast cancer known for its poor prognosis and its resistance to conventional treatments. TNBC is more primed to respond to immunotherapy given the presence of more tumor infiltrating lymphocytes, higher PD-L1 expression, and higher tumor mutation burden relative to the other breast cancer subtypes, and therefore, immuno-oncology represents a key area of promise for TNBC research. The aim of this review is to highlight current data and ongoing efforts to establish the safety and efficacy of immunotherapeutic approaches beyond checkpoint inhibitors in TNBC.

Fig. 1. Immuno-oncology (IO) agents in development for breast cancer and triple-negative breast cancer (TNBC).

a Number of IO agents in active development that are being explored in breast cancer and TNBC. “Checkpoint inhibitor” category includes only PD-1, PD-L1, and CTLA-4 targeted agents, while other immunomodulators that fall outside of “vaccine”, “adoptive cell therapy”, “oncolytic virus”, “cytokine therapy”, and “T cell engagers” are grouped into “other immunomodulators”. These include immunomodulators to natural killer cells, B cells, and other immune cells. b Most common targets of IO agents explored in breast cancer, where only targets with at least three agents in active development are shown. TAA tumor-associated antigens.

Fig. 2. Clinical trials for triple-negative breast cancer using IO agents as of March 2022 data pull from clinicaltrials.gov database.

a Number of clinical trials at various study phases across different types of IO therapy. b Number of trials using various IO therapies from 2008 to present (*incomplete 2022 trials due to data pull date). Line graph represents patient enrollment for each indicated year.