Postmenopausal Advanced Breast Cancer: Options for Therapy After Tamoxifen and Aromatase Inhibitors

Breast. 2006 Oct;15(5):584-94. doi: 10.1016/j.breast.2006.01.007. Epub 2006 Feb 28.


All patients receiving endocrine treatment for advanced breast cancer (ABC) eventually progress, resulting in a need for new therapies that lack cross-resistance with existing agents. Oestrogen receptor (ER) modulators such as toremifene and raloxifene have poor efficacy following tamoxifen failure, whereas the non-steroidal aromatase inhibitors (AIs), anastrozole and letrozole and the steroidal AI exemestane are effective. Fulvestrant is a new ER antagonist with no agonist effects that is as effective as anastrozole in treating patients who have progressed on tamoxifen. AIs are replacing tamoxifen as first-line treatments for ABC and in the adjuvant setting, necessitating a re-evaluation of optimal sequencing. Preliminary data suggest that tamoxifen, exemestane and fulvestrant have activity in patients who have progressed on non-steroidal AIs and hence could be considered for use in this setting. Due to the apparent lack of cross-resistance between non-steroidal and steroidal AIs, non-steroidal AIs could also be effective following steroidal AI failure. Clinical trials are underway to assess the most appropriate treatment sequence following non-steroidal AI failure, with comparisons of fulvestrant and exemestane of major interest.

Publication types

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

MeSH terms

  • Aromatase Inhibitors / administration & dosage
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Decision Trees
  • Drug Resistance, Neoplasm*
  • Estradiol / analogs & derivatives*
  • Estradiol / therapeutic use
  • Estrogen Receptor Modulators / therapeutic use*
  • Female
  • Fulvestrant
  • Humans
  • Postmenopause
  • Raloxifene Hydrochloride / administration & dosage
  • Tamoxifen / administration & dosage


  • Aromatase Inhibitors
  • Estrogen Receptor Modulators
  • Tamoxifen
  • Fulvestrant
  • Raloxifene Hydrochloride
  • Estradiol