ERalpha-negative and triple negative breast cancer: molecular features and potential therapeutic approaches

Abstract

Triple negative breast cancer (TNBC) is a type of aggressive breast cancer lacking the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER-2). TNBC patients account for approximately 15% of total breast cancer patients and are more prevalent among young African, African-American and Latino women patients. The currently available ER-targeted and Her-2-based therapies are not effective for treating TNBC. Recent studies have revealed a number of novel features of TNBC. In the present work, we comprehensively addressed these features and discussed potential therapeutic approaches based on these features for TNBC, with particular focus on: 1) the pathological features of TNBC/basal-like breast cancer; 2) E(2)/ERbeta-mediated signaling pathways; 3) G-protein coupling receptor-30/epithelial growth factor receptor (GPCR-30/EGFR) signaling pathway; 4) interactions of ERbeta with breast cancer 1/2 (BRCA1/2); 5) chemokine CXCL8 and related chemokines; 6) altered microRNA signatures and suppression of ERalpha expression/ERalpha-signaling by micro-RNAs; 7) altered expression of several pro-oncongenic and tumor suppressor proteins; and 8) genotoxic effects caused by oxidative estrogen metabolites. Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC.

Figures

Figure 1. Molecular Features of TNBC: 1)

E2/ERβ-mediated signaling pathways and Interaction with BRCA1; 2) E2/GRCP-30/EGFR signaling pathway; 3) CXCL8 and related CXC Chemokines; 4) MicroRNA signatures; 5) Notch/Suvivin; 6) Akt; 7) E-cadherin/E-Selectin and 8) Osteoponin are shown. Basic shapes filled with colors indicate increased expression; Basic shapes filled without color [148] indicate loss or reduced levels of the indicated proteins/receptors