Abstract 3853: Genomic profiling of circulating tumor DNA in endometrial cancer in Asia: A-TRAIN study.

Abstract Background: Endometrial cancer affects more than 420,000 women worldwide, with approximately 40% of cases occurring in Asia. Recently, endometrial cancer is now more precisely categorized through molecular subtyping, which has improved prognostic assessment and guided treatment strategies. In this study, we identified molecular subtypes of endometrial cancer in Asian patients using comprehensive genomic profiling of liquid biopsy samples, circulating tumor DNA (ctDNA). Methods: This is an Asian multicenter prospective observational study conducted by five institutions in Japan, Malaysia, Philippines, Taiwan, and Thailand (NCT05099978, ClinicalTrials.gov). Eligible patients had histological diagnosis of endometrial cancer with metastatic or recurrent disease. Genomic profiling was conducted by AmpliSeq HD custom panel (Thermo Fisher Scientific), targeting 23 genes (752 amplicons), designed using AmpliSeq Designer to cover on genes and hotspot mutation regions associated with endometrial cancer. This panel can identify (1) full-length in following genes: ARID1A, ARID1B, B2M, CCNE1, CTCF, JAK1, PIK3R1, PTEN, RB1, RPL22, SMARCB1, SMARCA4 and TP53, (2) hotspot mutation or region in following genes: AKT1, BRAF, CTNNB1, ERBB2, KRAS, MET, MYC, PIK3CA, POLE and PPP2R1A. Results: From August 2022 to March 2024, a total of 60 patients with advanced endometrial cancer were enrolled, including 44 from Japan, 10 from Taiwan, 3 from Malaysia, 2 from Philippines, and 1 from Thailand. The median age was 59 (range, 31 to 79) years. Most cases were at relapse (36; 60.0%) at liquid biopsy. In terms of therapy, 10 (16.7%) of the subjects had received radiation prior to the liquid biopsy, and 33 (55%) of the patients had received chemotherapy prior to the liquid biopsy. Genomic alterations were detected in 75.0% (45/60), with a median number of 2 genomic abnormality per case (range, 0-12). The most frequently altered genes were PTEN (n=20, 33.3%), TP53 (n=19, 31.7%), PIK3CA (n=19, 31.7%) and CTNNB1 (n=14, 23.3%). CNV analysis excluded 18 samples with both low coverage depth and low uniformity, or low uniformity alone, resulting in a total of 42 cases analyzed. CNVs were detected in eight patients: 2 with ERBB2 amplification, 2 with PIK3CA amplification, 2 with MYC amplification, and 2 with CCNE1 amplification. Conclusion: The comprehensive genomic profiling of liquid-based samples prior to treatment initiation may help guide personalized therapeutic strategies for Asian patients with advanced or recurrent endometrial cancer. Citation Format: Hiroki Tamura, Yuki Kojima, Kazuki Sudo, Wan Zamaniah Wan Ishak, Marcelo S. Imasa, Arb-aroon Lertkhachonsuk, Ryoka Miki, Hiroshi Yoshida, Shinji Kohsaka, Yukari Nagasaka, Ryunosuke Machida, Tetsuya Sasaki, Tomomi Hata, Kenichi Nakamura, Kan Yonemori. Genomic profiling of circulating tumor DNA in endometrial cancer in Asia: A-TRAIN study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3853.