Endocrine resistance in breast cancer: new roles for ErbB3 and ErbB4

Breast Cancer Res. 2011 May 20;13(3):106. doi: 10.1186/bcr2878.


Endocrine resistance is a major limitation to the successful treatment of estrogen receptor-positive (ER(+)) breast cancer, and the EGFR (epidermal growth factor receptor) and ErbB-2 receptor tyrosine kinases are involved in this process. A recent study now implicates the other two ErbB family members, ErbB-3 and -4. Exposure of ER+ breast cancer cells to the pure antiestrogen, fulvestrant, increased levels of ErbB-3 or ErbB-4 and sensitivity to the growth-stimulatory effects of heregulin β1, a potent ligand for these receptors. Thus, the initial growth-inhibitory effects of fulvestrant appear compromised by cellular plasticity that allows rapid compensatory growth stimulation via ErbB-3/4. Further evaluation of pan-ErbB receptor inhibitors in endocrine-resistant disease appears warranted.

Publication types

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

MeSH terms

  • ErbB Receptors / metabolism*
  • Estradiol / analogs & derivatives*
  • Female
  • Humans
  • Neuregulin-1 / metabolism*
  • Receptor, ErbB-3 / metabolism*


  • Neuregulin-1
  • Estradiol
  • ErbB Receptors
  • Receptor, ErbB-3