Triple negative breast cancer: unmet medical needs

Abstract

Triple negative breast cancer (TNBC) is an aggressive clinical phenotype characterized by lack of expression (or minimal expression) of estrogen receptor (ER) and progesterone receptor (PR) as well as an absence of human epidermal growth factor receptor–2 (HER2) overexpression. It shows substantial overlap with basal-type and BRCA1-related breast cancers, both of which also have aggressive clinical courses. However, this overlap is not complete, and the expression of ER, PR, and HER2 has been noted in basal-like tumors. TNBC also includes the normal-like subtype, and not all patients with TNBC harbor BRCA1 mutations. Because of its expression profile, TNBC is not amenable to treatment with hormone therapy or the anti-HER2 monoclonal antibody trastuzumab, and systemic treatment options are currently limited to cytotoxic chemotherapy. Overall survival, whether in early-stage or advanced disease, is poor compared with that in patients who have other phenotypes. A number of targeted approaches to TNBC are undergoing clinical evaluation, including the use of agents with poly(ADP-ribose) polymerase inhibitory properties such as iniparib (the United States Adopted Name for the investigational agent BSI-201), olaparib (AZD2281), and veliparib (ABT-888), antiangiogenic agents such as bevacizumab and sunitinib, and epidermal growth factor receptor blockers such as cetuximab and erlotinib. Encouraging results with some of these agents have been reported, thereby offering the promise for improved outcomes in patients with TNBC. The clinical characteristics of TNBC and clinical experience to date with novel targeted agents under development for this aggressive phenotype is reviewed.

Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer

“…There was also no significant association between subtypes and clinicopathological features, consistent with previous reports (18). In accordance to recent findings (19,20), the HER2-overexpressing subtype showed the worst OS and DFS, but the survival rate of patients with triple negative carcinomas was not different from that of other groups except for the HER2-overexpressing subtype. The luminal A group of patients showed an unexpectedly low OS and DFS.…”

AP-1 Is a Key Regulator of Proinflammatory Cytokine TNFα-mediated Triple-negative Breast Cancer Progression

“…Triple-negative breast cancer (TNBC), 3 which lacks expression of estrogen receptor (ER) and progesterone receptor (PR) as well as HER2 amplification, is more aggressive and has poorer survival than other types of breast cancer (1). TNBC is a clinically heterogeneous disease and accordingly, TNBC has recently been classified into five clusters, each harboring a dominant biological function/pathway (2).…”

Combination of Pan-Histone Deacetylase Inhibitor and Autophagy Inhibitor Exerts Superior Efficacy against Triple-Negative Human Breast Cancer Cells

“…TNBC cells often express genes characteristic of the basal epithelial and normal breast myoepithelial cells (27). TNBCs are associated with high rates of relapse following chemotherapy (28,29) Therefore, it is important to develop novel and effective therapies targeting TNBCs (28,29). Our studies show that, in vivo, advanced TNBC displays evidence for ER stress and autophagy.…”