Targeted inhibition of the HER2 pathway has dramatically enhanced survival rates among patients diagnosed with metastatic hormone receptor-negative, HER2-positive (HR−/HER2+) breast carcinoma. Nonetheless, the underlying influences guiding its clinical use are still not fully understood. This investigation explores clinical, demographic, and institutional predictors influencing the administration of HER2-focused treatments in individuals with metastatic HR−/HER2+ disease. Using the National Cancer Database (NCDB) covering years 2013-2020, a retrospective cohort design was employed. Participants were categorized according to whether they received HER2-directed therapy or not, with records lacking critical data removed. The study period was grouped into three segments—before 2015, 2016-2018, and 2019-2020—to mirror changes in therapeutic access across the U.S. Logistic regression (univariable and multivariable) identified determinants of treatment receipt, while survival was evaluated using Cox models and log-rank comparisons. Of 3060 individuals with metastatic HR−/HER2+ disease, 2318 (75.8%) underwent HER2-targeted therapy. Utilization climbed from 64.6% in 2013 to 80.9% by 2016, showing rapid early uptake, stayed elevated through 2018, and later stabilized near 75% between 2019 and 2020. Treatment receipt was more common among those diagnosed during 2016-2018 (OR 1.93, p < 0.001) and 2019-2020 (OR 1.88, p < 0.001), privately insured patients (OR 1.76, p < 0.001), and those managed at academic institutions (OR 1.39, p = 0.031). Lower odds were noted among patients aged ≥71 (OR 0.52, p < 0.001), Black patients (OR 0.78, p = 0.018), those covered by Medicare (OR 0.64, p < 0.001), and individuals treated in rural hospitals (OR 0.59, p = 0.022). Survival was significantly better for treated patients (median 5.08 vs. 1.27 years, log-rank p < 0.001), with reduced mortality risk (HR 0.52, p < 0.001). While uptake of HER2-targeted therapy has grown over time, measurable disparities in its distribution remain. Addressing socioeconomic and facility-related inequalities is crucial for equitable treatment access and improved outcomes across patient populations.
