激素依赖性（HR）转移性子宫内膜癌患者经常接受内分泌治疗。 ESR1 突变已成为 HR  转移性乳腺癌中芳香酶抑制剂 (AI) 耐药性的关键机制，并且可以使用循环肿瘤 DNA (ctDNA) 进行监测。本研究的目的是探讨接受 AI 或醋酸甲地孕酮 (M) 治疗的晚期子宫内膜癌患者中循环 ESR1 突变的发生率和临床相关性。这项单中心回顾性研究是在 Henri Becquerel 中心（鲁昂）和通过液滴数字 PCR（E380Q、L536R、Y537S、Y537N、Y537C、D538G、S463P）在 2008 年至 2020 年间接受 AI 或 M 治疗至少 30 天的晚期 HR  子宫内膜癌患者中寻找循环 ESR1 基因突变。暴露前和进展时/内分泌治疗期间。包括 22 名患者：13 人接受 AI 治疗，其中 12 人进展； 9 名患者接受了 M 治疗，其中 8 名病情进展。 68.1% 的患者患有低度子宫内膜癌，54.5% 的患者在转移性环境中接受过化疗。 AI 治疗的中位治疗持续时间为 152 天（最短 47 - 最长 629 天），M 治疗为 155 天（最短 91 - 最长 1297 天）。在 AI 治疗下，基线时没有 ESR1 突变，而进展时存在一种 Y537C 突变。等位基因频率 (VAF) 为 0.14%。在 M 治疗下，一名患者基线时有 Y537C (VAF 0.2%)，但在治疗期间消失。另一名患者在治疗 91 天后出现进展时出现 Y537S 突变（VAF 1.83%）。激素治疗前后循环DNA浓度无显着差异(p = 0.16)。ESR1突变似乎不参与HR子宫内膜癌对AI或M的抵抗机制。未证明其检测的临床相关性。© 2023。作者。

Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma.This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy.Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 - max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16).ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated.© 2023. The Author(s).