Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial...

Area of Science:

• Oncology
• Genetics
• Health Disparities

Background:

• Endometrioid endometrial carcinoma (EEC) disproportionately affects Black women, with existing data suggesting poorer outcomes.
• Understanding the molecular underpinnings and clinical presentation differences is crucial for addressing racial disparities in EEC.

Purpose of the Study:

• To investigate racial disparities in clinical outcomes and molecular features between Black and White patients diagnosed with EEC.
• To compare survival rates, disease characteristics, and genetic mutations in EEC patients across different racial groups.

Main Methods:

• Retrospective analysis of large patient cohorts from SEER, NCDB, GENIE, and NCI-sponsored randomized phase III clinical trials (RCTs).
• Utilized hazard ratios (HR) and propensity-score matching to compare cancer-related death (CRD), non-cancer death (NCD), and all-cause death between Black and White EEC patients.
• Analyzed mutation frequencies of key genes (e.g., PTEN, TP53) and tumor mutational burden (TMB) in relation to race.

Main Results:

• Black patients exhibited significantly higher risks of CRD and NCD compared to White patients in SEER and NCDB datasets.
• After propensity-score matching, Black patients still showed an increased risk of death, particularly in real-world data.
• Molecular analysis revealed fewer PI3K-pathway-related mutations but similar TP53 and DNA-repair gene mutation frequencies in Black patients.
• In RCTs, Black patients presented with more advanced disease, higher grade, and worse performance status, correlating with increased mortality risk.

Conclusions:

• Significant racial disparities exist in clinical presentation, outcomes, and molecular profiles for patients with EEC.
• Strategies including targeted drug development, addressing social determinants of health, and increasing diversity in clinical trials are essential to mitigate these disparities.