Northwestern Feinberg School of Medicine Chicago, IL
S. Zheng, E. D. Donnelly, and J. B. Strauss; Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL
Purpose/Objective(s): For endometrial cancer (EC) patients, Black race predicts poorer survival, even after adjusting for surgery, histology, grade, age, stage at diagnosis, comorbid conditions, access to care and socioeconomic factors. We and others recently reported that pathogenic POLE alterations are rare in Black EC patients. However, alternative biomarkers that may predict favorable outcomes for Black EC patients for treatment de-escalation are unknown. Materials/
Methods: This retrospective cohort study incorporated the largest available EC patients’ datasets including AACR Project GENIE (n=5,087), Memorial Sloan Kettering-Metastatic Events and Tropisms (n=1,315) and The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC, n=517). The prevalence and prognostic significance of POLE or POLD1 mutations in EC were evaluated across self-reported racial groups. Results: A total of 6,919 EC cases were studied, of whom 444, 694 and 4,869 patients were self-described as Asian, Black and White, respectively. Within these large data sets, Black patients with EC exhibited a lower weighted average prevalence of pathogenic POLE mutations (0.5%, 3 out of 590 cases), as compared to Asian (6.1%; 26 out of 424) or White (4.6%; 204 out of 4,520) patients. By contrast, the prevalence of POLD1 pathogenic mutations was 5.0%, 3.2%, and 5.6% in Asian, Black and White EC patients. Patients with POLD1 mutations exhibited an excellent prognosis regardless of race, histology and TP53 mutation status. Only 23% of POLE mutated cases co-existed with POLD1 mutations. Patients with both POLE/POLD1 mutated vs. POLE mutated alone vs. POLD1 mutated alone showed similar favorable survival rates (p=0.2). As compared with TCGA/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) EC risk classification algorithm, the composite biomarker panel of POLE or POLD1 mutations identified more Asian, Black and White EC good prognosis than using POLE alone (10% vs. 5.4%; 6.7% vs. 1.5%; 9.6% vs. 7.4%, respectively). Conclusion: In this retrospective clinicopathological study, we found while pathogenic POLE was uncommon in Black patients with EC, POLD1 mutations were evenly distributed across racial groups.A composite biomarker panel of either POLD1 or POLE mutation can potentially guide treatment de-escalation for more EC patients than using POLE alone, which is especially relevant for Black patients.
