Dynamic tumor microenvironment, molecular heterogeneity, and distinct immunologic portrait of triple-negative breast cancer: an impact on classification and treatment approaches

Abstract

Heterogeneity of the tumor microenvironment (TME) and the lack of a definite targetable receptor in triple-negative breast cancer (TNBC) has carved a niche for this cancer as a particularly therapeutically challenging form of breast cancer. However, recent advances in high-throughput genomic analysis have provided new insights into the unique microenvironment and defining characteristics of various subsets of TNBC. This improved understanding has contributed to the development of novel therapeutic strategies including targeted therapies such as PARP inhibitors and CDK inhibitors. Moreover, the recent FDA approval of the immune checkpoint inhibitor against programmed cell death protein 1 (PD-1), pembrolizumab and atezolizumab, holds the promise of improving the quality of life and increasing the overall survival of TNBC patients. This recent approval is one of the many therapeutically novel strategies that are currently being exploited in clinical trials toward eventual contribution to the oncologist's toolbox against TNBC. In this review, we comprehensively discuss TNBC's distinct TME and its immunophenotype. Furthermore, we highlight the histological and molecular classification of this cancer. More importantly, we describe how these characteristics and classifications contribute to the current standards of care and how they steer the development of newer and more targeted therapies toward achieving peak therapeutic goals in the treatment of TNBC.

Keywords: Immunotherapies; TNBC immunologic portraits; TNBC molecular heterogeneity; TNBC tumor microenvironment; Targeted therapies; Triple-negative breast cancer.