Possible mechanisms in the emergence of tamoxifen-resistant breast cancer

Anticancer Drugs. 1995 Aug;6(4):498-507. doi: 10.1097/00001813-199508000-00002.


Tamoxifen (TAM), a non-steroidal antiestrogen, is the endocrine treatment of choice for all stages of breast cancer. However, despite a favorable initial response to therapy, most tumors will eventually exhibit TAM resistance resulting in disease recurrence. Several mechanisms of TAM resistance have been proposed, yet a single distinct mechanism has not been identified. We will systematically consider the following steps of the estrogen receptor (ER)-mediated signal transduction pathway to identify possible sites of alteration leading to tamoxifen-resistance: (1) ligand metabolism and availability, (2) loss or mutation of the ER, (3) defects in ER post-translational modification, and (4) alteration of the estrogen response element (ERE). In particular, the ERE will be discussed as a position in the signal transduction pathway with considerable potential, if altered, to confer TAM resistance.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / physiopathology
  • Drug Resistance
  • Humans
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use*


  • Antineoplastic Agents, Hormonal
  • Tamoxifen