Systematic Next Generation Sequencing is feasible in clinical practice and identifies opportunities for targeted therapy in women with uterine cancer: Results from a prospective cohort study

• Published in: Gynecologic oncology 2021-10, Vol.163 (1), p.85-92
• Main Authors: Arend, Rebecca C., Goel, Nidhi, Roane, Brandon M., Foxall, McKenzie E., Dholakia, Jhalak, Londoño, Angelina I., Wall, Jaclyn A., Leath, Charles A., Huh, Warner K.
• Format: Article
• Language: English
• Subjects: Adult; African American; African Americans; Aged; Aged, 80 and over; Disparities; DNA-Binding Proteins - genetics; Female; Genes, p53; High-Throughput Nucleotide Sequencing - methods; Humans; Middle Aged; Molecular Targeted Therapy; Mutation; Next Generation Sequencing; Personalized medicine; Prospective Studies; Targeted therapies; Transcription Factors - genetics; Uterine cancer; Uterine Neoplasms - diagnosis; Uterine Neoplasms - drug therapy; Uterine Neoplasms - genetics
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2021.07.017

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. •Next Generation Sequencing is feasible in a uterine malignancy clinical workflow;•NGS for uterine malignancies provides guidance for targetable mutations and trials;•Incorporating NGS into clinical workflows may help address treatment disparities.