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 tack 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 (Als), anastrozole and letrozole and the steroidal Al 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. Als 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 Als and hence could be considered for use in this setting. Due to the apparent tack of cross-resistance between nonsteroidal and steroidal Als, non-steroidal Als could also be effective following steroidal Al failure. Clinical trials are underway to assess the most appropriate treatment sequence following non-steroidal Al failure, with comparisons of fulvestrant and exemestane of major interest. (C) 2006 Elsevier Ltd. All rights reserved.