Journal of Mammary Gland Biology and Neoplasia

, Volume 15, Issue 1, pp 35–47

Epigenetic Regulation in Estrogen Receptor Positive Breast Cancer—Role in Treatment Response

Authors

  • Thushangi N. Pathiraja
    • Translational Biology and Molecular Medicine Graduate Program, Lester and Sue Smith Breast CenterBaylor College of Medicine
  • Vered Stearns
    • Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins School of Medicine
    • Lester and Sue Smith Breast Center, Department of Medicine, and Department of Molecular and Cellular BiologyBaylor College of Medicine
Article

DOI: 10.1007/s10911-010-9166-0

Cite this article as:
Pathiraja, T.N., Stearns, V. & Oesterreich, S. J Mammary Gland Biol Neoplasia (2010) 15: 35. doi:10.1007/s10911-010-9166-0

Abstract

Recent advances in breast cancer treatment have allowed increasing numbers of patients with estrogen receptor (ER) positive (+) breast cancer to receive various forms of endocrine therapy. Unfortunately, de novo and acquired resistance to endocrine therapy remains a major challenge in the clinic. A number of possible mechanisms for drug resistance have been described, which include activation of growth factor receptor pathways, overexpression of ER coactivators, and metabolic resistance due to polymorphisms in metabolizing enzymes. While many of these changes are caused by genetic alterations, there is also increasing evidence to implicate epigenetic gene regulatory mechanisms in the development of endocrine resistance. Since epigenetic modifications are easier to reverse than genetic mutations, they are appealing therapeutic targets, and thus future improvements in medical care for breast cancer patients will depend upon a better understanding of the roles epigenetic modifications play in endocrine resistance. In this review we will focus on recent advances made in the understanding of epigenetic gene regulation in estrogen response and endocrine resistance in breast cancer. We will also summarize current clinical-translational advances in epigenetic therapy, and discuss potential future clinical use of epigenetic changes as therapeutic targets, especially with respect to endocrine treatment.

Keywords

EpigeneticsBreast cancerEstrogenAntiestrogenTamoxifen

Abbreviations

ER

estrogen receptor

PR

progesterone receptor

HDAC

histone deacetylase

SERM

selective estrogen receptor modulators

AI

aromatase inhibitor

Copyright information

© Springer Science+Business Media, LLC 2010