ABSTRACT
I. ABSTRACT Tamoxifen has been used to treat advanced breast cancer for 30 years and has been the first-line endocrine therapy of choice for much of this period. It is well tolerated and inexpensive, and serious side effects are uncommon. Survival rates are equivalent to those from chemotherapy, and although initial response rates are lower, it offers a superior quality of life in initial responders. Tamoxifen should not be displaced as a key therapy for advanced breast cancer without substantial and convincing data from large randomized trials. Response rates depend on patient selection and are higher for patients with estrogen-responsive tumors. Tamoxifen alone has efficacy similar to that of estrogens or progestins when used singly or in combination, but it is better tolerated than most alternative endocrine therapies. In premenopausal patients there is good evidence that the combination of tamoxifen and a luteinizing hormone-releasing hormone (LHRH) analogue is superior to either single agent alone. This benefit of combination endocrine therapy with tamoxifen will not necessarily be translated to postmenopausal patients. Recently, third-generation aromatase inhibitors have been compared with tamoxifen in postmenopausal patients with advanced breast
cancer and have been shown to have possibly superior efficacy, with reduced side effects. This opens up new, potentially beneficial strategies using combined endocrine therapies-concurrently and in sequence in both pre-and postmenopausal patients. Given the sequential benefits demonstrated for tamoxifen from advanced to in situ disease and prevention for over 30 years, it seems very likely that aromatase inhibitors will be shown to be effective in all types of endocrine-responsive breast cancer. Future clinical trials testing endocrine therapies in advanced breast cancer should be large, have similar defined populations and biological endpoints, and involve intergroup collaborations similar to those established for adjuvant trials. This is essential to avoid taking another 30 years to evaluate newer endocrine therapies.
