University of Alabama in Birmingham, Division of Gynecologic Oncology, Birmingham, AL, United States of America.
University of Alabama School of Medicine, Birmingham, AL, United States of America.
Gynecol Oncol. 2021 Oct;163(1):85-92. doi: 10.1016/j.ygyno.2021.07.017. Epub 2021 Aug 6.
Both incidence and mortality of uterine cancer are on the rise and mortality is higher for African American women. The aim of our study was to evaluate how Next Generation Sequencing (NGS) may facilitate identification of and intervention for treatment disparities when integrated into clinical workflows.
Our cohort included 159 uterine cancer patients with recurrent/progressive and newly diagnosed advanced stage and/or high-risk histology. The most common tumor histological subtypes included EEC (n = 67), SEC (n = 34), UCS (n = 20), and mixed (n = 14). Black patients were most likely to present with aggressive histology: (SEC, 34.0%) and carcinosarcoma (UCS, 14.0%). The four most common mutations across all subtypes were TP53, PIK3CA, PTEN, and ARID1A. There was racial disparity between Black versus non-Black patients who were initiated on targeted therapy (28.2% vs. 38.2%, respectively) and clinical trial (15% vs. 22.6%, respectively). Compared to non-Black patients, Black patients had a significantly higher percentage TP53 mutations (p < 0.05) and a significantly lower percentage ARID1A mutations (p < 0.05).
NGS for uterine malignancies provides actionable information for targetable mutations and/or clinical trial enrollment in most patients; further investigation is necessary to identify potentially modifiable factors contributing to current disparities that may improve targeted therapy uptake and clinical trial participation.
子宫癌的发病率和死亡率都在上升,且非裔美国女性的死亡率更高。我们的研究旨在评估下一代测序(NGS)如何在整合到临床工作流程中时,促进治疗差异的识别和干预。
我们的队列包括 159 名患有复发性/进行性和新诊断的晚期和/或高危组织学的子宫癌患者。最常见的肿瘤组织学亚型包括 EEC(n=67)、SEC(n=34)、UCS(n=20)和混合(n=14)。黑人患者最有可能出现侵袭性组织学:SEC(34.0%)和癌肉瘤(UCS,14.0%)。所有亚型中最常见的四个突变是 TP53、PIK3CA、PTEN 和 ARID1A。在开始接受靶向治疗(分别为 28.2%和 38.2%)和临床试验(分别为 15%和 22.6%)的黑人患者与非黑人患者之间存在种族差异。与非黑人患者相比,黑人患者的 TP53 突变百分比显著更高(p<0.05),ARID1A 突变百分比显著更低(p<0.05)。
NGS 用于子宫恶性肿瘤为大多数患者提供了针对可靶向突变和/或临床试验入组的可操作信息;需要进一步研究以确定导致当前差异的潜在可改变因素,这可能会提高靶向治疗的接受率和临床试验的参与率。