The aromatase inhibitors (AIs), letrozole (Femar®/Femara®) and exemestane (Aromasin®), are widely used to treat estrogen receptor (ER) positive breast cancer in postmenopausal patients. In the setting of metastatic breast cancer, these drugs may be used after another causing new responses in selected patients after progressing on the first choice. The precise explanation for this "lack of cross resistance" is still missing. NEOLETEXE is a neoadjuvant, randomized, open-label, cross-over trial. Postmenopausal patients with ER-positive, HER-2 negative, locally advanced breast cancer were enrolled. All patients were randomized to treatment starting with either letrozole or exemestane for at least 2 months followed by another 2 months on the alternative AI. The total estrogenic activities in blood samples were determined using the AroER tri-screen assay developed in the Chen laboratory. Using this highly sensitive assay, estrogenic activity was detected at three time points for all patients. Importantly, a significantly higher total estrogenic activity was found during therapy with exemestane compared to letrozole in 21 out of 26 patients. When letrozole was included in the AroER tri-screen assay, the estrogenic activities in most samples collected during exemestane treatment were further reduced, suggesting that low levels of androgens remained in specimens obtained after exemestane treatment. Our results suggest the AroER tri-screen to be a very sensitive method to estimate the overall estrogen-mediated activity in human samples even during therapy with highly potent aromatase inhibitors. In the present study, serum estrogen activity was significantly higher during exemestane therapy when compared to letrozole therapy.

中文翻译：

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来曲唑和依西美坦新辅助治疗期间血清雌激素活性的变化。

芳香酶抑制剂（AIs），来曲唑（Femar®/Femara®）和依西美坦（Aromasin®）被广泛用于治疗绝经后患者的雌激素受体（ER）阳性乳腺癌。在转移性乳腺癌的情况下，这些药物可能会先后使用，在选定的患者中依次使用，引起新的反应。这种“缺乏交叉阻力”的精确解释仍然缺失。NEOLETEXE是一项新辅助，随机，开放标签，交叉试验。纳入了ER阳性，HER-2阴性，局部晚期乳腺癌的绝经后患者。所有患者均随机分组接受来曲唑或依西美坦治疗至少2个月，然后再使用替代AI 2个月。使用在Chen实验室开发的AroER三筛选测定法测定血液样品中的总雌激素活性。使用这种高度灵敏的测定法，在所有患者的三个时间点检测到雌激素活性。重要的是，在26个患者中有21个患者在依西美坦治疗期间发现总的雌激素活性高于来曲唑。当将来曲唑包括在AroER三筛选试验中时，在依西美坦治疗期间收集的大多数样品中的雌激素活性进一步降低，这表明经依西美坦治疗后获得的样品中雄激素含量较低。我们的结果表明，即使在使用强力芳香化酶抑制剂治疗期间，AroER三联筛查也是一种非常敏感的方法，可以评估人类样品中总体雌激素介导的活性。