Search

Introduction Triple-negative breast cancer (TNBC) is considered the most aggressive breast cancer subtype with the least favorable outcomes. However, recent research efforts have generated an enhanced knowledge of the biology of the disease and have provided a new, more comprehensive understanding of the multifaceted ecosystem that underpins TNBC. Areas covered In this review, the authors illustrate the principal biological characteristics of TNBC, the molecular driver alterations, targetable genes, and the biomarkers of immune engagement that have been identified across the subgroups of TNBC. Accordingly, the authors summarize the landscape of the innovative and investigative biomarker-driven therapeutic options in TNBC that emerge from the unique biological basis of the disease. Expert opinion The therapeutic setting of TNBC is rapidly evolving. An enriched understanding of the tumor spatial and temporal heterogeneity and the surrounding microenvironment of this complex disease can effectively support the development of novel and tailored opportunities of treatment.

Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.