This cohort study used first-in-kind linkage of Surveillance, Epidemiology, and End Results, Medicare, and residual tumor repository data of 3522 women with newly diagnosed screening- vs symptomatic-detected estrogen receptor–positive nonmetastatic breast cancer to demonstrate that screening and socioeconomic factors remain associated with breast cancer outcomes, even after adjusting for clinical, demographic, and genomic factors. This evidence concerns the gene ESR1 and breast carcinoma.