Inability of medroxyprogesterone acetate to down regulate estrogen receptor level in human breast cancer

The influence of medroxyprogesterone acetate (MPA) on estrogen receptor (ER) and progesterone receptor (PR) levels was studied in 20 postmenopausal patients with ER-positive and PR-positive primary breast cancers. Each patient underwent drill biopsy and subsequently mastectomy. The drill biopsy and surgical specimens were assayed for the total ER and PR levels (cytosolic plus nuclear fraction) by enzyme immunoassay. Between the drill biopsy and mastectomy, ten patients received no treatment (control group) and the other ten patients were given MPA (1200 mg/day) for 7 days. In the control group, the total ER and PR levels of the surgical specimens decreased by 68.2 +/- 7.3% and 60.7 +/- 8.4%, respectively, taking the receptor values of the drill biopsy specimens as 100%, although no treatment was given preoperatively. This decrease seems to be attributable to the receptor degradation due to damages occurring during mastectomy. In the MPA group, the total ER and PR levels of the surgical specimens decreased by 64.2 +/- 8.0% and 23.3 +/- 7.6%, respectively. The decrease in PR, but not ER, was statistically significant between the control and MPA groups (P less than 0.01). These results demonstrate that MPA down regulates PR but not ER in human breast cancer and challenge the conventional idea, extrapolated from the results on the endometrium and endometrial cancer, that MPA antagonizes endogenous estrogens by down regulating ER.