PROGESTINS AND BREAST-CANCER

In the last years there has been an extraordinary development in the s ynthesis of new progestins. These compounds are classified, in agreeme nt with their structure, in various groups which include progesterone, retroprogesterones, 17 alpha-hydroxyprogesterones, 19-norprogesterone s, 17 alpha-hydroxyprogesterone derivatives, androstane and estrane de rivatives. The action of progestins is a function of many factors: its structure, affinity to the progesterone receptor or to other steroid receptors, the target tissue considered, the biological response, the experimental conditions, dose, and metabolic transformation. The infor mation on the action of progestins in breast cancer patients is very l imited. Positive response with the progestins: medroxyprogesterone ace tate and megestrol acetate was obtained in post-menopausal patients wi th advanced breast cancer. However, extensive information on the effec t of progestins was obtained in in vitro studies using hormone-depende nt and hormone-independent human mammary cancer cell lines. It was dem onstrated that in the hormone-dependent breast cancer cells, various p rogestins (nomegestrol acetate, tibolone, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involv e the inhibition of mRNA of this enzyme. In another series of studies it was also demonstrated that various progestins are very active in in hibiting the 17 beta-hydroxysteroid dehydrogenase for the conversion o f estrone to estradiol. More recently it was observed that the progest ins promegestone or medrogestone stimulate the sulfotransferase for th e formation of estrogen sulfates. Consequently, the blockage in the fo rmation of estradiol via sulfatase, or the stimulatory effect on sulfo transferase activity, by progestins can open interesting and new possi bilities in clinical applications in breast cancer. (C) 1998 Elsevier Science Ltd. All rights reserved.