Racial and ethnic disparities in clinical outcomes of HER2-positive metastatic breast cancer treated with antibody-drug conjugates

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Abstract
Background: Antibody–drug conjugates have substantially improved outcomes for patients with HER2-positive (HER2+) metastatic breast cancer. Whether these survival gains have translated equitably across racial and ethnic groups remains unclear despite persistent disparities in breast cancer outcomes. Methods: We conducted a retrospective cohort study using de-identified electronic health record data from the TriNetX Research Network (2010-2024). Adults with HER2+ metastatic breast cancer treated with trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) were included. Overall survival was estimated using Kaplan–Meier methods and compared across racial and ethnic groups. Multivariable Cox models adjusted for age, body mass index, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, and prior lines of therapy. Results: The cohort included 7462 patients with HER2+ metastatic breast cancer: 5072 non-Hispanic White (68%), 1193 Black (16%), 746 Hispanic (10%), and 298 Asian (4%). Five-year overall survival was highest among Asian (89.9%) and Hispanic (86.3%) patients, followed by non-Hispanic White (84.0%) and Black patients (80.3%) (P < .001). Compared with non-Hispanic White patients, Black patients experienced worse overall survival (adjusted hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P = .03). Survival differences among Asian and Hispanic patients were not observed after multivariable adjustment. Conclusions: Among patients with HER2+ metastatic breast cancer treated with HER2-directed antibody–drug conjugates, Black patients experienced persistently inferior survival despite receipt of effective therapies. These findings highlight ongoing inequities and underscore the need for interventions to ensure equitable translation of therapeutic advances across all populations.

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