J Breast Cancer.  2018 Sep;21(3):233-243. 10.4048/jbc.2018.21.e41.

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

• Temian DC
• Pop LA
• Irimie AI
• Berindan-Neagoe I

• KMID: 2421363
• DOI: http://doi.org/10.4048/jbc.2018.21.e41

Abstract

Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies-the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis-DNA methylation, histone modifications, and noncoding RNAs-advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Keyword

Breast neoplasms; DNA methylation; Histone code; Triple negative breast neoplasms; Untranslated RNA

MeSH Terms

Breast Neoplasms*
Breast*
Diagnosis
DNA Methylation
Epigenomics*
Female
Histone Code
Humans
Incidence
Methylation
Prognosis
RNA, Untranslated
Triple Negative Breast Neoplasms
RNA, Untranslated

Figure

• 

  Figure 1 Classification systems developed for triple-negative breast cancer (TNBC). (A) Intrinsic subtypes of breast cancer, first established in 2001 by Sørlie et al. [5]. This classification is most widely used by both clinicians and researchers due to numerous confirmed prognostic, predictive and therapeutic correlations. The pie chart represents the distribution of these intrinsic subtypes among the imunohistochemically defined TNBC, the majority being represented by basal-like tumors. (B) TNBCtype-4 comprised of six subtypes was established in 2011 by Lehmann et al. [12] and subsequently redefined to TNBCtype-4 in 2016 [13]. The pie chart represents the distribution of these subtypes among TNBC, again the majority being represented by basal-like tumors. ER=estrogen receptor; PR=progesterone receptor; HER2=human epidermal growth factor receptor 2; BL=basal-like; M=mesenchymal; LAR=luminal androgen receptor; EGF=epidermal growth factor; NGF=nerve growth factor; MET=tyrosine-protein kinase Met encoded by the MET gene; IGF1R=insulin-like growth factor 1 receptor.

• 

  Figure 2 Patterns of methylation described in triple-negative breast cancer. Hypermethylation of CpG islands and shores with hypomethylation of intragenic regions leads to epigenetic silencing. At nucleosomal level the patterns in DNA methylation translate to tri-methylation of lysine 27 on histone H3 (H3K27me3), another marker of epigenetic silencing.

• 

  Figure 3 HOTAIR in basal-like breast cancer. HOTAIR forms a complex with the enhancer of zeste homolog 2 (EZH2) subunit of the polycomb repressor complex 2 (PRC2) complex, which leads to H3K27 trimethylation and maintenance of the basal-like phenotype. H3K27me3=tri-methylation of lysine 27 on histone H3.

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