Racial disparities and nonconcordance with endocrine and HER2 therapy for breast cancer: A sequential mediation analysis of neighborhood deprivation and insurance status.

1647 Background: Racial disparities in breast cancer treatment persist, but the mechanisms driving inequities may differ by therapy type. We evaluated whether neighborhood racialized economic segregation (mediator 1, M1) and insurance status (M2) sequentially mediate racial disparities in receipt of guideline-concordant endocrine and anti-HER2 therapy. Methods: We conducted a retrospective cohort analysis of women diagnosed with breast cancer using the Florida Cancer Data System (2013–2021). Eligible women included those with invasive, nonmetastatic disease with hormone or HER2-receptor-positive tumors. Treatment nonconcordance was defined as failure to receive recommended systemic therapy based on tumor receptor status. M1 was measured by the racial-income version of the Index of Concentration at the Extremes (ICE) at the census tract level and divided into quintiles from the most to least deprived. Insurance status was categorized as insured versus Medicaid/uninsured/unknown (MUU). Simple frequencies were obtained to assess the relationships between race, the mediators, and therapy nonconcordance. Causal mediation analyses using the parametric g-formula quantified natural course risks and the proportion of the racial disparity mediated by ICE and insurance status, while adjusting for confounders (disease stage, molecular subtype [endocrine only], tumor grade, age, region of the state, and marital status). Results: There were 71,077 and 3,021 women available for the analysis of endocrine and HER2 therapy, respectively. For nonconcordance with endocrine therapy, disparities were present by race (37.2% vs. 29.0%, Black vs. White), the ICE (37.2% vs. 26.2%, most vs. least deprived), and insurance status (36.1% vs. 29.4%, MUU vs. other). Smaller disparities were present for nonconcordance with HER2 therapy by race (18.1% vs. 12.9%, Black vs. White), the ICE (16.2% vs. 14.2%, most vs. least deprived), and insurance status (18.5% vs. 13.4%, MUU vs. other). In causal mediation analysis for nonconcordance with endocrine therapy, the natural course counterfactual risks showed a 5% absolute disparity by race (34.3% vs. 29.3%); 59% of this disparity was mediated by the ICE and insurance status. For nonconcordance with HER2 therapy, the natural course counterfactual risks showed a 4% absolute disparity by race (17.1% vs. 13.1%); none of this disparity was mediated by the ICE and insurance status. Conclusions: Racial disparities in receipt of endocrine therapy are largely mediated by neighborhood deprivation and access to care, whereas these factors played no role in explaining disparities in anti-HER2 therapy. These findings suggest that treatment disparities are therapy-specific and that analyses of aggregate treatment outcomes may obscure distinct mechanisms of inequity.