Reproducibility of the correlation between race and outcomes associated with treatment of HER2+ breast cancer across databases.

e13769 Background: HER2-positive (HER2+) breast cancer (BrCa) is an aggressive subtype, accounting for 20–30% of all BrCa cases. Trastuzumab, a monoclonal anti-HER2 antibody, remains the cornerstone of treatment. Previously, we identified race as a factor associated with increased toxicities and poorer outcomes in HER2+ BrCa treatment using the TriNetX database. Methods: In this propensity score-matched cohort study, we used the TriNetX Research Network to compare mortality rates in non-Hispanic African American (NHAA) and non-Hispanic White (NHW) women with HER2+ BrCa. Cohorts were matched for age, BMI, comorbidities, and laboratory values using 1:1 matching with a greedy nearest neighbor search. To assess the robustness of the results based on the TriNetX data, we compared overall mortality after diagnosis between matched NHAA and NHW cohorts using patient-level data from the SEER and NCDB databases. Results: SEER data indicated that NHAA women had 1.48 times higher odds of death compared to NHW women. NCDB data showed NHAA women had 1.36 times higher odds of death, while TriNetX data revealed 1.10 times higher odds. We examined the effect of marital status and education on mortality, finding that being married and living in areas with higher education levels were associated with lower odds of mortality. Mortality odds decreased as education level increased, with the highest level of education showing the greatest protective effect. The influence of these proxies for socioeconomic status was independent of race. Conclusions: Our findings demonstrate increased odds of mortality for NHAA compared to NHW patients with HER2+ BrCa undergoing Trastuzumab therapy across all three databases. We identified social factors, including education and marital status, as independent predictors of mortality in HER2+ BrCa patients. The consistency of mortality findings across databases supports the reliability of our previous TriNetX results, confirming that NHAA women with HER2+ BrCa face higher odds of mortality and toxic effects compared to their NHW counterparts. Effect of marital status on mortality while adjusting for gender, age, stage of disease, and race using SEER. Marital Status Odds Ratio (95% CI) Interpretation Divorced (Reference) - Baseline group for comparison Married (including common law) 0.75 [0.68, 0.83] 25% lower odds of death compared to divorced individuals Separated 1.19 [0.87, 1.62] Not significantly different from divorced individuals Single (never married) 1.18 [1.04, 1.34] 18% higher odds of death compared to divorced individuals Unknown 1.27 [1.06, 1.53] 27% higher odds of death compared to divorced individuals Unmarried/Domestic Partner 0.73 [0.37, 1.44] Not significantly different from divorced individuals Widowed 1.52 [1.34, 1.73] 52% higher odds of death compared to divorced individuals