Targeted inhibition of HER2 has transformed the management of metastatic hormone receptor–negative, HER2-positive (HR−/HER2+) breast cancer and substantially extended survival. Despite these advances, real-world patterns of treatment delivery and the factors shaping access to HER2-directed therapies are incompletely characterized. This study investigates patient-, social-, and facility-level characteristics associated with the receipt of HER2-targeted therapy in metastatic HR−/HER2+ breast cancer. Using the National Cancer Database, we identified patients diagnosed with metastatic HR−/HER2+ breast cancer between 2013 and 2020. Individuals were grouped according to whether they received HER2-targeted therapy, with exclusion of cases missing essential covariates. The study period was divided into three eras (pre-2015, 2016–2018, and 2019–2020) to reflect changes in therapeutic availability and clinical practice in the United States. Logistic regression analyses were performed to determine factors independently associated with treatment receipt. Overall survival was analyzed using Kaplan–Meier methods, log-rank testing, and Cox proportional hazards models. Among 3,060 eligible patients, 2,318 (75.8%) received HER2-targeted therapy. Treatment adoption increased sharply early in the study period, rising from 64.6% in 2013 to 80.9% by 2016, after which utilization plateaued and modestly declined, stabilizing near 75% during 2019–2020. More recent year of diagnosis, private insurance coverage, and care at academic institutions were independently associated with higher odds of receiving HER2-targeted therapy. In contrast, advanced age (≥71 years), Black race, Medicare insurance, and treatment at rural facilities were linked to lower treatment likelihood. Patients treated with HER2-targeted therapy experienced markedly superior outcomes, with substantially longer median survival (5.08 vs. 1.27 years) and a significantly reduced risk of death. Although HER2-targeted therapies are now widely incorporated into the treatment of metastatic HR−/HER2+ breast cancer, meaningful inequities in their use persist. Disparities related to age, race, insurance status, and treatment setting continue to influence access to these life-prolonging therapies. Efforts to reduce structural and systemic barriers are essential to ensure equitable treatment delivery and optimize outcomes across all patient populations.
