The effects of
antiestrogens,
tamoxifen and
ICI 182,780, and
aromatase inhibitors,
arimidex (
anastrozole ZD1033) and
letrozole (CGS 20,267), on the growth of
tumors were studied in nude mice. In this model,
estrogen dependent MCF-7 human
breast cancer cells stably transfected with the
aromatase gene were inoculated in four sites per mouse. Sufficient
estrogen is produced from aromatization of
androstenedione supplement (0.1 mg/mouse/day) by the cells to stimulate their proliferation,
tumor formation, and maintain the uterus similar to that of the intact mouse. Once the
tumors reached a measurable size, the mice were injected with
antiestrogen or inhibitor for 35-56 days.
Tumor volumes were measured weekly. At autopsy, the
tumors were removed, cleaned, and weighed. Statistical data was determined from
tumor weights. Both
antiestrogens were effective in reducing
tumor growth in these mice.
Tamoxifen appears to be more effective than
ICI 182,780, although the former stimulated the uterine weight whereas the pure
antiestrogen did not. However, both
aromatase inhibitors were more effective than the
antiestrogens.
Tumor regression was observed with
letrozole. Thus,
after-treatment tumor weights were less than those of a group of mice at the start of treatment. The
aromatase inhibitors also reduced the weight of the uterus, suggesting that these compounds, as well as the pure
antiestrogen, may not cause endometrial proliferation, unlike
tamoxifen. These
aromatase inhibitors may not only benefit patients who have relapsed from
tamoxifen, but may be more effective in patients as first line agents for suppressing the effects of
estrogen.