Figure 1.

The use of the dimethyl benzanthracene (DMBA)-induced rat mammary carcinoma model to demonstrate that longer or continuous therapy with daily tamoxifen (50μg subcutaneous injection) was superior at preventing the appearance of mammary tumors when compared to short therapy of 30 days. Fifty day old female Sprague Dawley rats were each given 20mg DMBA by gavage in 2 mls peanut oil. In nontreated control groups of 20 animals, all rats had multiple palpable tumors by 150 days. The model design for therapy groups first administered the DMBA at 50 days of age but the 30 day or continuous treatment was delayed for 30 days to permit mammary carcinogenesis of initiation and promotion to occur. The goal was to establish whether a short 30 day course of tamoxifen (estimated to be equivalent to 1 year of adjuvant tamoxifen in patients) could destroy the deranged microscopic cancer cells in the mammary glands or whether continuous therapy was required for complete tumor control and suppression. Continuous therapy is necessary. The strategy was to use tamoxifen only in the patients with ER positive tumors (Jordan and Koerner 1975) and use continuous therapy. This new strategy was first reported at the King College Cambridge, ICI Pharmaceuticals Division, Medical Symposium September 1977.