Tamoxifen resistance: from cell culture experiments towards novel biomarkers

Pathol Res Pract. 2015 Mar;211(3):189-97. doi: 10.1016/j.prp.2015.01.004. Epub 2015 Jan 21.


Tamoxifen is still the most frequently used antiestrogen for the treatment of patients with premenopausal, estrogen receptor positive breast cancer. However, in 20-30% of these cases, tamoxifen therapy fails due to an existing or developing resistance. The prediction of tamoxifen resistance by appropriate biomarker analysis and the development of novel therapies for tamoxifen resistance in premenopausal breast cancer is, therefore, an important goal of ongoing research. Tamoxifen resistance is associated with altered estrogen receptor expression especially on the plasma membrane, including the alternative G-protein coupled receptor GPR-30 (GPER) and estrogen receptor splice products, such as ERα36. Tamoxifen resistant cells often use alternative pathways to promote proliferation in the absence of genomic estrogen signaling. These pathways involve the epidermal growth factor EGF, the inflammation associated transcription factor NF-κB- and the IGF-1 pathway. Tamoxifen resistant mamma carcinoma cell lines are useful models to understand tamoxifen resistance in-vitro and to search for prognostic or predictive biomarkers. Furthermore, such cell lines can be used to identify potential targets for therapy.

Keywords: Advanced glycation end products; Breast cancer; Estrogen receptor; GPER; IGF1-receptor; Tamoxifen.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Tamoxifen / therapeutic use*
  • Treatment Failure


  • Antineoplastic Agents, Hormonal
  • Biomarkers
  • Receptors, Estrogen
  • Tamoxifen