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Review
. 2020 May 8;9(5):1164.
doi: 10.3390/cells9051164.

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Flavia Lima Costa Faldoni  1   2 , Cláudia Aparecida Rainho  3 , Silvia Regina Rogatto  4
Affiliations
Review

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Flavia Lima Costa Faldoni et al. Cells. .

Abstract

Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d'orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.

Keywords: DNA methylation; epigenetic therapy; histone deacetylases; histone modifications; inflammatory breast cancer.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Epigenetic regulation of gene expression. (A) DNA methylation, histone modifications, and noncoding RNAs modulate the chromatin accessibility and gene expression. In cancer, dysregulated histone marks and DNA hypermethylation contribute to epigenetic silencing of tumor suppressor genes. Epigenetic regulation is a dynamic and reversible process mediated by enzymes termed “writers” and “erasers”. Inherent reversibility of epigenetic changes and aberrant epigenetic marks are promising anticancer strategies based on inhibitors targeting these enzymes (DNMTs—DNA methyltransferases, HATs—histone acetyltransferases, HKMTs—histone lysine methyltransferases, HDACs—histone deacetylases, HKDMs—histone lysine demethylases, TETs—ten-eleven translocation family proteins, TSS—transcription start site, DNMTi, HKMTi, HDACi—inhibitors of DNMTs, HKMTs or HDACs, respectively). The image was performed with Mind the Graph (mindthegraph.com).
Figure 2
Figure 2
(A) Effects of genetic ancestry and environmental exposures on racial/ethnic disparities of IBC (inflammatory breast cancer) incidence. (B) Changes in DNA methylation have been associated with risk factors such as obesity, chronic inflammation, and environmental exposure. Venn diagram shows the overlapping between genomic ancestry and environmental exposure on differential methylation in ethnic subgroups associated with the risk of IBC development (central area in dark red). (C) Accumulation of genetic and epigenetic alterations drive tumor progression and contribute to the heterogeneity and plasticity of cancer cells. Epigenetic changes also provide new opportunities for chemoprevention and biomarkers’ development. (CAFs, cancer-associated fibroblasts; MSCs, mesenchymal stem cells; BPA, bisphenol A; DES, diethylstilbestrol). The image was performed using Mind the Graph (mindthegraph.com).
See this image and copyright information in PMC

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