OBJECTIVES: There is a paucity of updated literature on the total direct costs of breast cancer (BC) from a US managed care perspective. This study was conducted to analyze the economic burden of BC with a focus on direct health care cost in the US. METHODS: This was a retrospective matched cohort study using a large claims database from a US national commercially-insured population (January 1, 2003-September 30, 2008). Women aged ≥18 were selected with ≥2 BC diagnoses on different dates within 90 days. The date of the first BC diagnosis was the index date for case cohort. The control cohort (without BC diagnosis) was selected with a 3:1 ratio by matching to the cases based on index date (same year and month), age (5-year range), region, employer, and health insurance type. Both cohorts were required to have continuous enrollment for at least 6-months prior to and 12-months after the index date. Generalized linear model (GLM) was applied to evaluate the 1-year post-index cost difference between cases and controls with adjustment of demographics, comorbid conditions, and pre-index total health care cost. RESULTS: Based on the selection criteria, 140,228 patients were included with mean (SD) age of 52.1 (7.5) years. The total 1-year health care costs for cases and controls were $61,167 and $6,296, respectively (p<0.001). GLM predicted that the adjusted incremental health care cost was $42,401 (p<0.001) per BC patient per year, which included 12%, 86%, and 2% for inpatient, outpatient, and prescription use. CONCLUSIONS: This study demonstrated that breast cancer is an expensive disease condition, which consumes on average $40,000 more per patient within the first year of diagnosis for the US health care system. Most of the direct health care cost is spent in outpatient care settings.