Selective oestrogen receptor modulators, aromatase inhibitors and the female breast

Tamoxifen has been available for over 20 years and remains the most commonly recognized endocrine therapy. This review was prompted by a wealth of new data on several newer endocrine agents, including selective oestrogen receptor modulators, aromatase inhibitors and a new oestrogen receptor antagonist, fulvestrant, which unlike the selective oestrogen receptor modulators has no oestrogen agonist effects.

Completed analysis of the 'Arimidex', Tamoxifen, Alone or in Combination trial demonstrated that anastrozole as initial adjuvant therapy significantly improved disease-free survival and time to recurrence compared with tamoxifen, as well as reducing the incidence of contralateral breast cancer deaths. The Italian Tamoxifen Anastrozole trial and the Austrian Breast and Colorectal Cancer Study Group 8/Arimidex Nolvadex 95 trial have indicated that anastrozole may also be beneficial in women who have already received 2-3 years of tamoxifen. Similarly, the Intergroup Exemestane Study demonstrated the efficacy of exemestane in this setting. Women who have completed a full 5-year course of tamoxifen may also benefit from aromatase inhibitor treatment as indicated by the MA 17 trial, which investigated letrozole as extended adjuvant therapy. Fulvestrant is effective in tamoxifen-resistant disease, and phase II trial data suggest that fulvestrant may also be effective following aromatase inhibitor failure.

The introduction of the third-generation aromatase inhibitors has caused a paradigm shift in adjuvant endocrine treatment. Research into the optimal use of selective oestrogen receptor modulators continues and the evidence base for fulvestrant, the first in a new class of endocrine agents, continues to grow, confirming its value in the treatment of hormone-responsive breast cancer.