Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence

Abstract

Triple-negative breast cancer (TNBC) is a kind of breast cancer that lacks estrogen, progesterone, and human epidermal growth factor receptor 2. This cancer is responsible for more than 15-20% of all breast cancers and is of particular research interest as it is therapeutically challenging mainly because of its low response to therapeutics and highly invasive nature. The non-availability of specific treatment options for TNBC is usually managed by conventional therapy, which often leads to relapse. The focus of this review is to provide up-to-date information related to TNBC epidemiology, risk factors, metastasis, different signaling pathways, and the pathways that can be blocked, immune suppressive cells of the TNBC microenvironment, current and investigation therapies, prognosis, and the role of artificial intelligence in TNBC diagnosis. The data presented in this paper may be helpful for researchers working in the field to obtain general and particular information to advance the understanding of TNBC and provide suitable disease management in the future.

Keywords: artificial intelligence; prognosis; risk factor; signaling pathways; triple negative breast cancer.

FIGURE 1

Schematic representation of Notch receptor activation and avenues for therapeutic intervention. The pathway is activated by ligand binding to Notch receptor, followed by proteolytic cleavage fy proteases. This releases the Notch intracellular domain, which is then transferred to nucleus for biding with C protein binding factor 1/Suppressor of Hairless/Lag-1 allowing conversion of complex from repressor to activator of Notch genes. From inhibition perspective, γ-secretase inhibitors and monoclonal antibodies can inhibit Notch ligands and receptors (Yuan et al., 2015; Medina et al., 2020).

FIGURE 2

A schematic illustration of epidermal growth factor receptor signaling pathway along with activators and inhibitors. The pathway is part of ErbB superfamily. The epidermal growth factor receptor is able to bind to different ligands at the extracellular surface resulting in the activation of downstream signaling events. Therapeutics including monoclonal antibodies and different kinase inhibitors can block the binding of ligand to the receptor. The kinase inhibitors can also block the function of other ErbB receptors (Ali and Wendt, 2017; Medina et al., 2020). Inhibitors of polyadenosine diphosphate-ribose polymerase.

FIGURE 3

Inhibition of poly (ADP-ribose) polymerase in BRCA-1/2-associated and sporadic cancers (Ellisen, 2011; Medina et al., 2020).

FIGURE 4

The mTor pathway illustrating two distinct complexes (mTORC1 and mTORC2). The pathway is stimulated by different growth factors. The mTORC2 activated Akt. Multiple cell functions are regulated by both mentioned complexes that are considered vital for cancer development. Also, in the figure different steps of the pathway that can be blocked by inhibitors are shown (Xie et al., 2016; Medina et al., 2020).

FIGURE 5

Different TME targets for therapeutic intervention.