Núñez Nomelí P, Jelovac Danijela, Macedo Luciana, Berrigan David, Perkins Susan N, Hursting Stephen D, Barrett J Carl, Brodie Angela
Division of Cancer Prevention, Cancer Prevention Fellowship Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland 20892-8325, USA.
Clin Cancer Res. 2004 Aug 15;10(16):5375-80. doi: 10.1158/1078-0432.CCR-04-0261.
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.
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.
As reported previously, tumor growth was markedly inhibited by both tamoxifen (100 microg/day) and letrozole (10 microg/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.
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.
本研究旨在评估并比较抗雌激素药物他莫昔芬和芳香化酶抑制剂来曲唑对小鼠肿瘤生长、血清激素、子宫重量、身体组成及骨骼特征的影响。
将稳定转染芳香化酶基因的人雌激素依赖性乳腺癌细胞（MCF-7CA细胞）接种于基质胶中，皮下植入去卵巢裸鼠体内。该模型在许多方面代表绝经后乳腺癌，包括卵巢不再产生雌激素且不受促性腺激素反馈调节这一事实。然后，对皮下植入MCF-7CA癌细胞的小鼠用他莫昔芬或来曲唑治疗7周。
如先前报道，他莫昔芬（100微克/天）和来曲唑（10微克/天）均显著抑制肿瘤生长。他莫昔芬治疗导致骨矿物质密度（BMD）增加及子宫增生。来曲唑治疗的小鼠子宫明显小于对照组及他莫昔芬治疗的小鼠。来曲唑不影响BMD。他莫昔芬或来曲唑治疗后，全身瘦素和胰岛素样生长因子I水平无显著差异。
在这个绝经后乳腺癌临床前模型中，他莫昔芬治疗抑制乳腺癌细胞生长并增加BMD，但导致子宫肥大。来曲唑抑制肿瘤生长且不诱导子宫肥大。此外，来曲唑对BMD无影响。这些发现提供了实验证据，表明来曲唑是他莫昔芬治疗乳腺癌的一种有效且安全（就子宫内膜癌风险和骨质疏松风险而言）的替代或补充药物。
