The role of progestins in the treatment of breast cancer.

In unselected populations of women, the progestins medroxyprogesterone acetate (MPA) and megestrol acetate (MA) have produced response rates of 14% to 31% in metastatic breast cancer, sparking new investigative activity to define their proper role. One proposed mechanism of action for progestins is that they interfere with replenishment of the cytoplasmic estrogen receptor. Although not binding to estrogen receptors, progesterone has been shown to decrease the quantity of estrogen receptor in target tissue. Prediction of response of metastatic breast cancer to progestins largely follows the conventional rules established for the selection of additive hormonal therapy. Little difference is seen between appropriate doses of MPA and of MA in reports of prognostic factors associated with tumor response. The presence of hormone receptors in tumor tissue may be the most significant predictor for response to progestins. Tumors that contain both estrogen and progesterone receptors will respond to progestins in over 61% of instances, whereas those with only one type of hormone receptor will respond 20% to 30% of the time. Response to MPA or MA is probably independent of the presence of progesterone receptor. Response rates to MA of around 30% have been noted in patients who had previously responded to tamoxifen and then progressed. Previous exposure to chemotherapy does not appear to jeopardize chances for response to MA. A limited number of randomized trials of tamoxifen versus MA show no significant response difference between the two therapies in breast cancer patients with similar prognoses.