GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients
GPER-1 expression is associated with a decreased response rate to primary tamoxifen therapy of breast cancer patients
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DOI：
10.1007/s00404-019-05384-6
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发表时间：
2020-02-01
影响因子：
2.6
通讯作者：
Ignatov, Atanas
中科院分区：
文献类型：
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作者：
Ignatov, Tanja;Treeck, Oliver;Ignatov, Atanas
目的使用他莫昔芬和/或芳香化酶抑制剂的内分泌疗法是靶向治疗对乳腺癌有反应的乳腺癌的重要治疗选择。除了核雌激素受体ER α和β外，G蛋白偶联雌激素受体GPER-1是乳腺癌细胞中介导雌激素效应的第三种受体。本研究的目的是研究GPER-1表达在多大程度上可能影响乳腺癌原发性内分泌治疗的疗效。方法应用免疫组化方法检测早期乳腺癌组织中GPER-1的表达，GPER-1评分≥ 3分为阳性。在总共165例患者中，通过超声成像评估了对他莫昔芬（TAM）或芳香酶抑制剂（AI）的主要治疗的反应，持续6个月。本研究的主要终点是根据RECIST 1.1标准评价的治疗应答。结果165例乳腺癌中127例（77.0%）表达GPER-1。根据GPER-1表达和内分泌治疗类型将患者分为4组：GPER-1阴性/TAM（12.1%）、GPER-1阴性/AI（10.9%）、GPER-1阳性/TAM（44.8%）和GPER-1阳性/AI（32.1%）。各组在不同的临床和病理因素方面平衡良好。治疗4个月和6个月后，仅在GPER-1阳性/TAM组中观察到高水平的疾病稳定或疾病进展（p < 0.0001），而在其他三组患者中，最常见的客观反应被归类为部分反应。我们观察到芳香化酶抑制剂治疗的患者的平均肿瘤大小的持续减少，无论GPER-1的状态和GPER-1阴性的患者与TAM治疗。相比之下，在接受TAM治疗的GPER-1阳性患者中，仅在治疗开始后的前2个月内观察到平均肿瘤大小减小。治疗开始后4个月和6个月，在该患者组中观察到肿瘤大小没有减少，但甚至略有增加。结论GPER-1表达与乳腺癌患者三苯氧胺初治疗效降低显著相关。
Purpose Endocrine therapies using tamoxifen and/or aromatase inhibitors are important therapeutic options for the targeted treatment of hormone-responsive breast cancer. In addition to nuclear estrogen receptors ER alpha and beta, G-protein-coupled estrogen receptor GPER-1 is a third receptor-mediating estrogen effects in breast cancer cells. The aim of this study was to examine to what extent GPER-1 expression might affect the efficacy of primary endocrine treatment of breast cancer. Methods GPER-1 expression was determined in tissue samples from patients with early breast cancer by means of immunohistochemistry and a GPER-1 score of >= 3 was considered to be positive. In a total of 165 patients, the response to a primary therapy with tamoxifen (TAM) or aromatase inhibitors (AI) was assessed by ultrasound imaging for up to 6 months. The primary endpoint of this study was the response to treatment evaluated by RECIST 1.1 criteria. Results GPER-1 expression was observed in 127 (77.0%) out of 165 cases. Based on GPER-1 expression and the type of endocrine treatment, the patients were divided into 4 groups: GPER-1 negative/TAM (12.1%), GPER-1 negative/AI (10.9%), GPER-1 positive/TAM (44.8%), and GPER-1 positive/AI (32.1%). The groups were well balanced regarding different clinical and pathological factors. After 4 and 6 months of treatment, a high level of stable disease or progressive disease was observed in the GPER-1 positive/TAM group only (p < 0.0001), whereas in the other three groups of patients, the most common objective response was classified as partial response. We observed a continuous reduction of mean tumor size in patients treated with aromatase inhibitors irrespective of the GPER-1 status and in GPER-1 negative patients treated with TAM. In contrast, in GPER-1 positive patients treated with TAM, a reduction of mean tumor size was observed only in the first 2 months after beginning of treatment. Four and six months after start of treatment, no reduction, but even a slight increase of tumor size was observed in this patients group. Conclusions GPER-1 expression is significantly associated with a reduced effect of primary treatment with tamoxifen in breast cancer patients.