Biological effects of progestins in breast cancer

Abstract

Developments in the synthesis of different progestins have opened up new possibilities for the biological effects and therapeutic uses of these compounds. The actions of progestins are a function of theirstructure ,affinity to the progesterone receptor or to other steroid receptors ,the target tissue considered ,the biological response ,the experimental conditions ,dose ,and metabolic transformation. Dataon the action of progestins in breast cancer patients are very limited. A positive response with the progestins medroxyprogesterone acetate and megestrol acetate has been obtained in postmenopausal patientswith advanced breast cancer. However ,extensive information on the effect of progestins was obtained in in vitro studies using hormone-dependent and hormone-independent human mammary cancer celllines. It was demonstrated that in hormone-dependent breast cancer cells ,various progestins (nomegestrol acetate ,medrogestone ,promegestone) as well as tibolone ,are potent sulfatase-inhibitory agents.Progestins may also be involved in the inhibition of the mRNA of this enzyme. In another series of studies ,it was also demonstrated that various progestins are very active in inhibiting the 17 β-hydroxysteroiddehydrogenase for the conversion of estrone to estradiol. More recently ,it has been observed that promegestone or medrogestone stimulates the sulfotransferase for the formation of estrogen sulfates. Clinicaltrials of these enzymatic effects on the formation and transformation of estradiol in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.