Signaling pathways and steroid receptors modulating estrogen receptor α function in breast cancer

Genes Dev. 2018 Sep 1;32(17-18):1141-1154. doi: 10.1101/gad.316646.118.


Estrogen receptor α (ER) is the major driver of ∼75% of breast cancers, and multiple ER targeting drugs are routinely used clinically to treat patients with ER+ breast cancer. However, many patients relapse on these targeted therapies and ultimately develop metastatic and incurable disease, and understanding the mechanisms leading to drug resistance is consequently of utmost importance. It is now clear that, in addition to estrogens, ER function is modulated by other steroid receptors and multiple signaling pathways (e.g., growth factor and cytokine signaling), and many of these pathways affect drug resistance and patient outcome. Here, we review the mechanisms through which these pathways impact ER function and drug resistance as well as discuss the clinical implications.

Keywords: breast cancer; cross-talk; cytokines; estrogen receptor; growth factors.

Publication types

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

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cytokines / physiology
  • Drug Resistance, Neoplasm
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology
  • Receptors, Steroid / metabolism*
  • Signal Transduction* / drug effects
  • Transcription Factors / metabolism


  • Cytokines
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Steroid
  • Transcription Factors