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Estrogen receptor beta (ERβ) was described already some 15 years ago, but received much less attention than ERα. Like ERα, ERβ is a member of the nuclear receptor superfamily of proteins that functions as a ligand-mediated transcription factor. The DNA binding domains of ERα and ERβ share 96% homology at the amino acid level; however, the remainder of the protein domains is highly divergent. About three-quarters of breast tumors express ERα, which is therefore the major marker that determines therapy with either selective estrogen receptor modulators (SERMs) or aromatase inhibitors. While ERβ is highly expressed in normal breast tissue, a number of immunohistochemistry-based studies have demonstrated conflicting data with regard to ERβ expression in breast tumors [1]. Also, the association between ERβ and disease recurrence, disease-free survival, overall survival and prognosis is conflicting. Reese and colleagues [1] examined three patient cohorts: 184 women who underwent primary breast cancer surgery (retrospective analysis); 68 patients who underwent primary breast cancer surgery selected for having a triple-negative breast cancer (TNBC) (retrospective analysis); and 258 eligible patients enrolled into a prospective adjuvant tamoxifen study in postmenopausal women with early-stage ERα-positive breast cancer. Their results revealed that expression of ERβ1 (one of several isoforms of ERβ), while detected in nearly all normal breast epithelium, is lost in many breast cancer tissues. However, the expression of ERβ1 is associated with substantially improved anti-tumor effects in ERα-positive tamoxifen-treated breast cancer, as well as potent anti-proliferative effects [i]in vitro[/i], confirming its role as a tumor suppressor. To note, ERβ1 was expressed in both ERα-positive and ERα-negative (TNBC) breast tumors.


  • Amos Pines
    Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel


  1. Reese JM, Suman VJ, Subramaniam M, et al. ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer. BMC Cancer 2014;14:749
  2. Huang B, Omoto Y, Iwase H, et al. Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer. Proc Natl Acad Sci USA 2014;111:1933-8
  3. Hinsche O, Girgert R, Emons G, Grundker C. Estrogen receptor β selective agonists reduce invasiveness of triple negative breast cancer cells. Int J Oncol 2015;46:878-84
  4. Ruddy SC, Lau R, Cabrita MA, et al. Preferential estrogen receptor β ligands reduce Bcl-2 expression in hormone-resistant breast cancer cells to increase autophagy. Mol Cancer Ther 2014;13:1882-93
  5. Guo L, Zhu Q, Yilamu D, Jakulin A, Liu S, Liang T. Expression and prognostic value of estrogen receptor beta in breast cancer patients. Int J Clin Exp Med 2014;7:3730-3736
  6. Leitman DC, Christians U. MF101: a multi-component botanical selective estrogen receptor beta modulator for the treatment of menopausal vasomotor symptoms. Expert Opin Investig Drugs 2012;21:1031-42
  7. Hapangama DK, Kamal AM, Bulmer JN. Estrogen receptor β: the guardian of the endometrium. Hum Reprod Update 2014 Oct 10. Epub ahead of print
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