The selective estrogen enzyme modulator (SEEM) in breast cancer

Human breast cancer tissue contains all the enzymes (estrone sulfatase, 17 beta -hydroxysteroid dehydrogenase, aromatase) involved in the last steps o f estradiol biosynthesis. This tissue also contains sulfotransferase for th e formation of the biologically inactive estrogen sulfates. In the last yea rs, it was demonstrated that various progestins (promegestone, nomegestrol acetate, medrogestone), as well as tibolone and its metabolites are potent inhibitors of sulfatase and 17 beta -hydroxysteroid dehydrogenase activitie s. It was also shown that medrogestone, nomegestrol acetate, promegestone o r tibolone can stimulate the sulfotransferase activity for the local produc tion of estrogen sulfates. All these data, in addition to numerous agents, which can block the aromatase action, lead to the new concept of selective estrogen enzyme modulators (SEEM), which can largely apply to breast cancer tissue. The exploration of various progestins and other active agents in t rials with breast cancer patients, showing an inhibitory effect on sulfatas e and 17 beta -hydroxysteroid dehydrogenase, or a stimulatory effect on sul fotransferase, will provide a new possibility in the treatment of this dise ase. (C) 2001 Elsevier Science Ltd. All rights reserved.