Tamoxifen--the treatment of choice. Why look for alternatives?

Abstract

Tamoxifen is currently established as the endocrine treatment of choice in breast cancer. In advanced breast cancer, response rates of up to 60% in women with oestrogen receptor (ER)-positive tumours have been reported. In early breast cancer, tamoxifen can produce significant benefits, both statistically and clinically, in terms of reduction in relative risk of relapse or death in all patient subgroups (i.e. ER status, aged < or > 50 years) except premenopausal women with ER-negative tumours. The major benefit, however, is seen in women over 50 years old with ER-positive tumours. The results of randomized trials suggest that the optimum duration of tamoxifen therapy is at least 5 years. Two large pragmatic trials (aTTom and ATLAS) are under way to determine whether additional benefit can be gained from continuing tamoxifen treatment beyond 5 years. Recent data also suggest possible synergism between tamoxifen and chemotherapy in the treatment of early breast cancer in post-menopausal women. Other benefits of tamoxifen treatment include reduction in the risk of developing contralateral breast cancer. Included among the non-breast cancer benefits of tamoxifen are reduced risk of cardiovascular disease and protection against bone loss in post-menopausal women. These benefits must be weighed against the possible increased incidence of endometrial cancer. Notwithstanding its undoubted success, there is a need for agents to improve upon tamoxifen. Newer agents, such as the luteinizing hormone-releasing hormone analogue goserelin and the new-generation aromatase inhibitors, such as anastrozole, will add new life to the search for an improved endocrine therapy for early breast cancer.