Treatment strategies using letrozole and tamoxifen in a xenograft model for breast cancer: Combined treatment versus alternating or sequential treatment

A tumor xenograft model has been established that more closely relates to hormone-dependent breast cancer than tumors induced with the carcinogens in the rat. The MCF-7Ca tumors are developed from MCF-7 cells transfected with aromatase. These cells synthesize estrogens and are responsive to the effects of estrogen via estrogen receptors. Tumor growth is inhibited by both aromatase inhibitors and antiestrogens. The purpose of these studies was to determine the effectiveness of several strategies of treatment with aromatase inhibitors and antiestrogens. Experiments have shown that tumor growth can be inhibited more effectively with aromatase inhibitors such as letrozole than with tamoxifen. Furthermore, the model demonstrated that an aromatase inhibitor alone is more effective than in combination with tamoxifen administered either together or sequentially. This result predicted the outcome of such clinical trials as ATAC (Arimidex and Tamoxifen Alone or in Combination) and suggests that the model is a good predictor of responses observed in human breast cancer patients. Thus, the model could be useful to guide the design of future clinical trials in patients with hormone-dependent breast cancer.