Postmenopausal advanced breast cancer: options for therapy after tamoxifen and aromatase inhibitors.
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.
Dodwell
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Cookridge Hospital, Leeds LS16 6QB, West Yorkshire, UK. david.dodwell@leedsth.nhs.uk
Wardley
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Johnston
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D047072:Aromatase Inhibitors / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003663:Decision Trees; D019008:Drug Resistance, Neoplasm; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage
D047072:Aromatase Inhibitors; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D000077267:Fulvestrant; D020849:Raloxifene Hydrochloride; D004958:Estradiol