Antiestrogens are efficient inhibitors of
estrogen-mediated growth of human
breast cancer. Besides inhibiting
estradiol-stimulated growth,
antiestrogens may have a direct growth-inhibitory effect on
estrogen receptor (ER) positive cells and thus be more efficient than
aromatase inhibitors, which will only abrogate
estrogen-dependent
tumor growth. To address this issue, we have used the human
breast cancer cell line MCF-7/S9 as a model system which is maintained in a chemically defined medium without serum and
estrogen. The addition of
estradiol results in an increase in cell growth rate. Thus, the MCF-7/S9 cell line is
estrogen-responsive but not
estrogen-dependent. Three different types of
antiestrogens, namely
tamoxifen,
ICI 182,780 and
EM-652 were found to exert a significant and dose-dependent inhibition of basal growth of MCF-7/S9 cells. The growth-inhibitory effect of the three
antiestrogens was prevented by simultaneous
estradiol treatment.
Antiestrogen treatment also reduced the basal pS2
mRNA expression level, thus indicating spontaneous estrogenic activity in the cells. However, treatment with the
aromatase inhibitor had no effect on basal cell growth, excluding that endogenous
estrogen synthesis is involved in basal growth. These data demonstrate that in addition to their
estrogen antagonistic effect,
antiestrogens have a direct growth-inhibitory effect which is ER-mediated. Consequently, in the subset of ER positive
breast cancer patients with
estrogen-independent
tumor growth,
antiestrogen therapy may be superior to treatment with
aromatase inhibitors which only inhibit
estrogen formation but do not affect
cancer cell growth in the absence of
estrogens.