Progestins in breast cancer treatment. A review.

The two most widely used synthetic progestins in breast cancer treatment, medroxyprogesterone acetate (MPA) and megestrol acetate (MA), are reviewed with regard to pharmacological, endocrinological and clinical aspects. In high oral doses as second- or first-line endocrine therapy in advanced breast cancer, they give a similar response rate as tamoxifen (TAM) and aminoglutethimide (AG). The mechanism of action is probably complex. Considerable changes in serum levels of different hormones are induced by progestin treatment. The decrease of serum estrone sulfate (E1S) may be part of the therapeutic mechanism. Some studies suggest that the two drugs, MPA and MA, have a different mode of action, and possibly a low cross resistance. Randomized studies using the two progestins with a cross-over design may answer these questions. Further studies on the influence of progestin on different receptors and growth factors are warranted. To determine the most effective clinical dose of the two progestins, studies with increasing therapeutic doses are needed.