Future directions in the endocrine therapy of breast cancer.

Data from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have indicated that anastrozole ('Arimidex') may supplant tamoxifen as the preferred adjuvant endocrine therapy for hormone receptor-positive, early breast cancer in postmenopausal women. The acceptability of this change in clinical practice at this time is currently under debate, and depends upon how confident we can be that 4 years' follow-up is sufficient to allow the overall risk:benefit balance to be assessed. The data supporting the benefits of sequential endocrine therapy are more certain, and if anastrozole does become the adjuvant agent of choice, the optimal sequence of endocrine agents will need to be identified for use after recurrence on anastrozole for early disease. It will be important that new endocrine options, such as the estrogen receptor antagonist fulvestrant ('Faslodex'), are suitably incorporated into these sequences. Developments such as the sequential use of endocrine therapies in the management of breast cancer have stimulated evolving concepts in our understanding of the basic cell biology of the disease. This has emphasized the importance of understanding the interactions between the different cell-signaling pathways that underlie the development of endocrine resistance. This will present a range of new opportunities for therapeutic intervention and will provide the foundation for the rational design of clinical trials. The resulting incorporation of more target-oriented approaches and newer endocrine agents into the treatment of breast cancer should stimulate the development of promising treatment paradigms and will ultimately provide further benefit to patients.