Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Differentiation / genetics
  • DNA Methylation / genetics
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Inflammatory Breast Neoplasms / epidemiology
  • Inflammatory Breast Neoplasms / genetics*
  • Inflammatory Breast Neoplasms / pathology
  • Inflammatory Breast Neoplasms / therapy*
  • Tumor Microenvironment