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

  • Thushangi N. Pathiraja
  • Vered Stearns
  • Steffi Oesterreich


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.


Epigenetics Breast cancer Estrogen Antiestrogen Tamoxifen 



estrogen receptor


progesterone receptor


histone deacetylase


selective estrogen receptor modulators


aromatase inhibitor

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Thushangi N. Pathiraja
    • 1
  • Vered Stearns
    • 2
  • Steffi Oesterreich
    • 3
  1. 1.Translational Biology and Molecular Medicine Graduate Program, Lester and Sue Smith Breast CenterBaylor College of MedicineHoustonUSA
  2. 2.Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins School of MedicineBaltimoreUSA
  3. 3.Lester and Sue Smith Breast Center, Department of Medicine, and Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonUSA

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