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

The effects of 17beta-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. 17beta-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 17beta-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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.