Letrozole is Superior to Anastrozole in Suppressing Breast Cancer Tissue and Plasma Estrogen Levels
Letrozole is Superior to Anastrozole in Suppressing Breast Cancer Tissue and Plasma Estrogen Levels
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DOI：
10.1158/1078-0432.ccr-07-5221
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发表时间：
2008-10-01
影响因子：
11.5
通讯作者：
Lonning, Per E.
中科院分区：
文献类型：
--
作者：
Geisler, Jurgen;Helle, Hilgegunn;Lonning, Per E.
目的：评价第三代芳香化酶抑制剂来曲唑（Femara）对局部晚期雌激素受体/孕激素受体阳性乳腺癌初治绝经后妇女乳腺癌组织中雌酮（El）、雌二醇（EA）和硫酸雌酮（E，S）水平的影响。实验设计：在来曲唑（2.5 mg o.d）辅助治疗4个月前和4个月后采集乳腺癌组织样本，高压液相色谱纯化后用高灵敏度RIA测定组织雌激素水平。结果：来曲唑对前期肿瘤E-2、E-1、E1S水平的抑制作用分别为97.6%、90.7%、90.1%。这些数据表明，来曲唑对组织雌激素水平的抑制明显低于先前使用相同方法的阿那曲唑（分别抑制89.0%，83.4%和72.9%）。为了证实来曲唑和阿那曲唑对血浆雌激素各组分的不同影响，我们使用改进的RIA （E-2、E-1和E1S的检出限分别为0.67、1.14和0.55 pmol/L）重新分析了从先前比较来曲唑和阿那曲唑的患者体内交叉研究中获得的血浆样本。来曲唑持续抑制血浆雌激素各部分低于阿那曲唑记录的水平：E-2（平均抑制95.2%对92.8%,P = 0.018）、E-1（平均抑制98.8%对96.3%,P = 0.003）和E1S（平均抑制98.9%对95.3%,P = 0.003）。结论：我们的数据显示，在绝经后乳腺癌患者中，来曲唑（2.5 mg o.d）比阿那曲唑（1.0 mg o.d）在组织和血浆雌激素抑制方面更有效。
Purpose:To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (El), estradiol (EA and estrone sulfate (E,S) in postmenopausal women undergoing primary treatment for locally advanced estrogen receptor/progester-one receptor - positive breast cancers.Experimental Design: Breast cancer tissue samples were collected before and following 4 months of neciadjuvant therapy with letrozole (2.5 mg o.d.), and tissue estrogen levels measured using a highly sensitive RIA after high-pressure liquid chromatography purification.Results: Letrozole suppressed pretreatment tumor levels of E-2, E-1, and E1S by 97.6%, 90.7%, and 90.1%, respectively. These data reveal that letrozole suppresses tissue estrogen levels significantly below what has previously been recorded with anastrozole (89.0%, 83.4%, and 72.9% suppression, respectively) using the same methods. To confirm the differential effect of letrozole and anastrozole on each plasma estrogen fraction, we re-analyzed plasma samples obtained from a previous intrapatient cross-over study comparing letrozole and anastrozole using an improved RIA (detection limits of 0.67,1.14, and 0.55 pmol/L for E-2, E-1, and E1S, respectively). Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E-2 (average suppression by 95.2% versus 92.8%; P = 0.018), E-1 (98.8% suppression versus 96.3%; P = 0.003), and E1S (98.9% suppression versus 95.3%; P = 0.003).Conclusion: Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.