Effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on serum hormones and bone characteristics in a preclinical tumor model for breast cancer

Purpose: The purpose of this study was to evaluate and compare the effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on tumor growth, serum hormones, uterine weight, body composition, and bone characteristics in mice. Experimental Design: Human estrogen-dependent breast cancer cells stably transfected with the aromatase gene (MCF-7CA cells) were inoculated in Matrigel subcutaneously into ovariectomized nude mice. This model represents postmenopausal breast cancer in many respects, including the fact that estrogen is no longer produced by the ovaries and is not under feedback regulation by gonadotropins. Mice that received subcutaneously implanted MCF-7CA cancer cells were then treated with tamoxifen or letrozole for 7 weeks. Results: As reported previously, tumor growth was markedly inhibited by both tamoxifen (100 μg/day) and letrozole (10 μg/day). Tamoxifen treatment led to increased bone mineral density (BMD) and hyperplastic uteri. Mice treated with letrozole had significantly smaller uteri than the controls and tamoxifen-treated mice. Letrozole did not affect BMD. There was no significant difference in systemic leptin and insulin-like growth factor I levels as a result of tamoxifen or letrozole treatment. Conclusions: Tamoxifen treatment inhibited breast cancer cell growth and increased BMD but caused uterine hypertrophy in this preclinical model of postmenopausal breast cancer. Letrozole inhibited tumor growth without inducing uterine hypertrophy. In addition, letrozole had no effect on BMD. These findings provide experimental evidence that letrozole is an effective and safe (in terms of risk of endometrial cancer risk and osteoporosis) alternative or complement to tamoxifen treatment for breast cancer.