Progestins and cancer

Abstract

The role of progestins in breast tissue is less well defined than in the endometrium. Although in vitro studies have shown that progestins induce a similar decrease in both estrogen and progesteronereceptors and an increase in 17β-estradiol dehydrogenase in the breast as in the endometrium ,epidemiologic studies have suggested that progestins prevent endometrial cancer ,but do not reversethe estrogen-related increase in breast cancer risk in long-term hormone-replacement therapy (HRT). Other studies have also suggested a protective effect for progestins on breast tissue.The dual effectof progesterone and progestins on the cell cycle has been demonstrated ,suggesting that according to the duration of administration ,the same steroid can induce cells to enter the multiplication phase orto enter a resting state.Progestins exert different effects according to the steroid from which they are derived ,e.g. pregnanes derived from progesterone ,estranes or gonanes derived from testosterone.Some estrane derivatives are able to stimulate breast cell multiplication in vitro through an estrogen receptor-mediated pathway. Most pregnanes do not exert such an effect. Also ,some pregnane derivativesstimulate apoptosis ,leading to cell death. However ,it is well established that high doses of progestins have been successfully used in the treatment of advanced breast cancer as second-line endocrinetherapy.Finally ,striking differences have been observed in progestin use in Europe and in the USA. In France ,where the rate of progestin use per head is higher than in the USA ,the rate of breastcancer has not increased as sharply as observed in North America.Although cancer genesis is multifactorial ,it may be concluded that progestins do protect endometrial tissue against the proliferativeaction of estrogen and if they do not protect breast tissue ,at least they do not stimulate its proliferation. Also ,they are useful agents as a second-line therapy for breast cancer ,when used at highdoses.