The future of new pure antiestrogens in clinical breast cancer

Summary The rationale for seeking to identify new pure antiestrogens was based on the recognition that existing antiestrogens, exemplified by tamoxifen, all possess partial agonist (estrogenic) activity. Conceptually, pure antiestrogens should be more effective than tamoxifen in ablating the mitogenic action of estrogens on breast tumor growth. The discovery and properties of the pure antiestrogens ICI 164,384 and ICI 182,780 are described and contrasted with those of tamoxifen. Key characteristics of these compounds which may be of particular relevance to their therapeutic application in the treatment of breast cancer are described. These include experimental data which predict efficacy in patients whose disease recurs during tamoxifen treatment, and the potential for pure antiestrogens to demonstrate greater efficacy than tamoxifen in first-line treatment of advanced breast cancer. The data imply that gains in efficacy could emerge as more rapid, more complete, or longer-lasting tumor remissions. Clinical trials with ICI 182,780 will reveal whether one or more of these predictions is correct.