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Updated: Jul 14, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Estrogen receptors outside the nucleus in breast cancer
Ellis R Levin1, Richard J Pietras
1University of California, Irvine/VA Long Beach Healthcare System, VALBHS, Long Beach, CA, USA. ellis.levin@va.gov
Abstract:
The estrogen receptor (ER) is the single most powerful predictor of breast cancer prognosis as well as an important contributor to the biology of carcinogenesis. In addition, endocrine therapy targeting ER directly (SERMS) or indirectly (aromatase inhibitors) forms the mainstay of adjuant therapy. Traditionally, human tumors are scored for the amount and presence of ER. However, this has centered on the population of ER found in the transformed epithelial cell nucleus. Over the last 40 years, it has been appreciated that additional cellular ER pools exist, in cytoplasm and at the plasma membrane. In this review, we discuss the important functions of extra-nuclear ER in breast cancer, including integration of function with nuclear ER.
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