Koskas Martin, Depreeuw Jeroen, Moens Stijn, Annibali Daniela, Cuppens Tine, Moerman Philippe, Lambrechts Diether, Amant Frederic
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, KU Leuven - University of Leuven, University Hospitals Leuven, Leuven, Belgium
Department of Obstetrics and Gynecology, APHP Hôpital Bichat, Diderot University Paris, Paris, France.
Anticancer Res. 2016 Oct;36(10):5381-5384. doi: 10.21873/anticanres.11112.
BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) positivity is associated with a worse prognosis in endometrial cancer (EC). Trastuzumab as a single agent did not demonstrate activity in such cases but there are no reports on its combined use with taxanes. We report the outcome in patients treated simultaneously with trastuzumab and paclitaxel for advanced or recurrent HER2-positive endometrial carcinoma and compared it to their microsatellite instability (MSI) status and PIK3CA mutational profiles.
Patients with advancedor recurrent endometrial carcinoma showing HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (fluorescence in situ hybridization (FISH) HER2/chromosome 17 centromere (CEP 17) ratio >2.0) were treated with trastuzumab (8 mg/kg) and paclitaxel (90 mg/m) every three weeks. Evaluation of the response was assessed according to the response evaluation criteria in solid tumors (RECIST) guidelines. Endometrial tumors, sampled before the beginning of trastuzumab, were genotyped for PIK3CA hot spot mutations using Sequenom iPLEX Assay technology.
Two uterine serous adenocarcinomas and one grade 3 endometrioid adenocarcinoma showing HER2 positivity were treated with trastuzumab and paclitaxel. Between three and seven months of treatment, the three cases showed progressive disease. The genomic analysis of the three cases showed different mutational profiles. One case was found to have MSI and had one PIK3CA mutation. The two others showed no hot spot mutation for PIK3CA.
Even associated with paclitaxel, HER2-positive endometrial carcinomas poorly responded to trastuzumab. This report underlines the low accuracy of HER2 positivity to predict response of endometrial cancer to combined targeted therapy using trastuzumab and paclitaxel.
背景/目的：人表皮生长因子受体2（HER2）阳性与子宫内膜癌（EC）预后较差相关。曲妥珠单抗单药治疗在这类病例中未显示出活性，但尚无其与紫杉烷类联合使用的报道。我们报告了曲妥珠单抗和紫杉醇同时治疗晚期或复发性HER2阳性子宫内膜癌患者的结果，并将其与微卫星不稳定性（MSI）状态和PIK3CA突变谱进行了比较。
晚期或复发性子宫内膜癌患者，若显示HER2过表达（免疫组化染色2+或3+）或HER2扩增（荧光原位杂交（FISH）检测HER2/17号染色体着丝粒（CEP 17）比值>2.0），每三周接受曲妥珠单抗（8 mg/kg）和紫杉醇（90 mg/m²）治疗。根据实体瘤疗效评价标准（RECIST）指南评估反应。在开始曲妥珠单抗治疗前采集的子宫内膜肿瘤样本，使用Sequenom iPLEX检测技术对PIK3CA热点突变进行基因分型。
2例子宫浆液性腺癌和1例3级子宫内膜样腺癌显示HER2阳性，接受了曲妥珠单抗和紫杉醇治疗。治疗3至7个月期间，3例均显示疾病进展。这3例的基因组分析显示出不同的突变谱。1例被发现为MSI，有1个PIK3CA突变。另外2例未发现PIK3CA热点突变。
即使与紫杉醇联合使用，HER2阳性子宫内膜癌对曲妥珠单抗的反应也较差。本报告强调了HER2阳性预测子宫内膜癌对曲妥珠单抗和紫杉醇联合靶向治疗反应的准确性较低。
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