Chukkalore Divya, Rajavel Anisha, Asti Divya, Dhar Meekoo
Department of Hematology/Oncology, Staten Island University Hospital, Staten Island, NY, United States.
Front Oncol. 2023 Jul 3;13:1188028. doi: 10.3389/fonc.2023.1188028. eCollection 2023.
The incidence of endometrial cancer is increasing, however treatment options for advanced disease are limited. Hormonal therapy has demonstrated positive outcomes for Stage IV EC. Next generation sequencing (NGS) has increased our understanding of molecular mechanisms driving EC. In this case series, we selected six patients at our institution with Stage IV, hormone receptor positive, endometrial cancer currently being treated with hormonal therapy. All patients achieved SD for at least ≥ 1.5 years. We studied NGS data on all six patients to assess for any common genomic marker which could predict the SD of at least 1.5 years achieved in this group. Institutional Review Board (IRB) approval was obtained from Staten Island University Hospital and Northwell Health, New York. PTEN, PIK3CA, PIK3R1, and ARID1A mutations were found in 83%, 67% 50%, and 67% of patients respectively. TP53 and FGFR2 were both found in 50% of patients. All patients were positive for estrogen and/or progesterone receptor (ER+ and/or PR+). We did not find any one common mutation that could have predicted the observed response (or SD of ≥1.5 years) to hormone therapy. However, our data reflects the prevalence of various mutations reported in literature: (1) Hormone Receptor status is a positive prognostic indicator (2) PTEN/PIK3CA mutations can occur concurrently in EC (3) ARID1A coexists with PTEN (4) FGFR and PTEN pathways may be interlinked. We suggest NGS be employed frequently in patients with endometrial cancer to identify targetable mutations. Additional larger studies are needed to characterize the interplay between mutations.
子宫内膜癌的发病率正在上升，然而晚期疾病的治疗选择有限。激素疗法已在IV期子宫内膜癌中显示出积极效果。下一代测序（NGS）增进了我们对驱动子宫内膜癌的分子机制的理解。在这个病例系列中，我们选择了本机构中6例IV期、激素受体阳性、目前正在接受激素治疗的子宫内膜癌患者。所有患者均达到疾病稳定（SD）至少≥1.5年。我们研究了所有6例患者的NGS数据，以评估是否存在任何可预测该组患者达到至少1.5年疾病稳定的常见基因组标志物。获得了纽约斯塔滕岛大学医院和诺斯韦尔健康中心机构审查委员会（IRB）的批准。分别在83%、67%、50%和67%的患者中发现了PTEN、PIK3CA、PIK3R1和ARID1A突变。TP53和FGFR2在50%的患者中均有发现。所有患者的雌激素和/或孕激素受体均为阳性（ER+和/或PR+）。我们未发现任何一种可预测对激素治疗观察到的反应（或≥1.5年的疾病稳定）的常见突变。然而，我们的数据反映了文献中报道的各种突变的发生率：（1）激素受体状态是一个积极的预后指标；（2）PTEN/PIK3CA突变可在子宫内膜癌中同时发生；（3）ARID1A与PTEN共存；（4）FGFR和PTEN途径可能相互关联。我们建议对子宫内膜癌患者频繁使用NGS来识别可靶向的突变。需要更多更大规模的研究来描述突变之间的相互作用。
