In vitro effects of estradiol, dydrogesterone, tamoxifen and cyclophosphamide on proliferation vs. death in human breast cancer cells.

The effects of 17 beta-estradiol, dihydrodydrogesterone, tamoxifen and cyclophosphamide upon parameters of cell maturation (Mucine1 expression), cell proliferation (Cyclin D1 expression) and apoptosis (loss of nuclear DNA) were studied in estrogen receptor positive (ER+) and negative (ER-) human breast cancer cells. Tamoxifen was the most potent inducer of apoptosis in ER+ and ER- breast cancer cells. 17 beta-estradiol in a concentration of 10(-6) M induced proliferation in ER+ cells after 144 h. incubation, while equimolar co-incubation with dihydrodydrogesterone prevented this effect and even induced a significant increase of cell death. It is speculated that the continuous use of combined 17 beta-estradiol plus dihydrodydrogesterone might be given as hormone replacement therapy without increased risk of breast cancer and even may reduce the relapse rate in breast cancer patients.