Importance of focal aromatase activity in hormone-dependent breast cancer:a review

The cytochrome P-450 enzyme complex aromatase is the rate-limiting step in the production of oestrogens. It catalyses the conversion of androgens to o estrogens. In the treatment of hormone-dependent breast cancer in postmenop ausal women, aromatase is the target for treatment with aromatase inhibitor s. Recently registered aromatase inhibitors like anastrozole, letrozole and exemestane have proven to be effective therapy for advanced breast cancer in postmenopausal patients failing to respond to treatment with tamoxifen. Intratumoural aromatase activity has predictive value for response to treat ment with aromatase inhibitors. Attempts are being made to find an immunohi stochemical technique to determine aromatase in tumour tissue, which may se rve as a predictive factor. In situ oestrogen synthesis through local aroma tase activity in the tumour and adjacent tissue is probably a very importan t growth-stimulating system in hormone-dependent breast cancer. This synthe sis can be blocked with aromatase inhibitors. The regulation of aromatase a ctivity and the cell types that contribute to this process are the subject of extensive research. There seems to be a complex interaction between mali gnant cells and adjacent cells ill which factors such as IL-6 and its solub le receptor, TNF-alpha and prostaglandin E2 play an important role in stimu lating aromatase activity. (C) 2001 Harcourt Publishers Ltd.