Abstract Background: Breast cancer is the most frequently diagnosed cancer in the United States, with 266,120 diagnoses in 2018. Detection and treatment have improved over time; the 5-year survival rate is 99% among those diagnosed with local disease (62% of all breast cancers), and 85% among those with regional disease (30% of all breast cancers). Nonetheless, recent evidence suggests that the lifetime risk of developing and dying from metastatic disease is substantial. Estimating population-level disease costs, including quality-adjusted life years prematurely lost and the societal willingness to pay to prevent that loss, can frame the value of research to decrease the incidence of breast cancer and the development of metastatic disease. Methods: We combined registry data from the National Cancer Institute’s SEER Program for 2012 through 2014 on diagnoses of invasive, non-metastatic breast cancer, and eliminated records (10%) with insufficient data to classify new diagnoses by hormone receptor (HR) status, human epidermal growth factor 2 (ERBB2), tumor size, tumor extension, and nodal status. We applied the distribution of patients with those characteristics to the cohort of 250,153 diagnosed with invasive, non-metastatic breast cancer in 2018. We noted that the median age at diagnosis was 62, and the average life expectancy of women of that age was 87. Given tumor characteristics, median life expectancy, and published annual rates of metastatic recurrence and survival with metastatic disease, we estimated the lifetime risk of developing metastatic breast cancer and dying from it for each member of the cohort. We subtracted age at death from average life expectancy to calculate years of life lost and quality-adjusted life-years lost to metastatic disease, and we used a standard willingness-to-pay threshold of $100,000 per quality-adjusted life-year to estimate the value of life lost to metastatic breast cancer among the 2018 cohort. We discounted years of life lost, quality-adjusted life-years lost and societal willingness to pay by 3% per year. Results: Among the 160,618 SEER records with sufficient data for analysis, 75% were HR+/ERBB2-, 11% were HR-/ERBB2-; 10% were HR+/ERBB2+, and 4% were HR-/ERBB2+. Regarding nodal status, 71% were N0, 22% N1, 5% N2, and 3% N3. Regarding tumor size, 60% were T1, 32% T2, 6% T3, and 3% T4. The overall lifetime risk of developing metastatic disease was 27%, while the risk of dying from it 23%. Extrapolating to all non-metastatic 2018 diagnoses, total undiscounted years of life lost for this annual cohort was 701,021, and total discounted years was 543,487. Undiscounted quality-adjusted life-years lost was 812,231, and discounted quality-adjusted life-years lost was 622,417. Societal willingness to pay to prevent discounted quality-adjusted life-years lost was $62.2 billion. Conclusions: Despite progress in the earlier detection of invasive, non-metastatic breast cancer and improvements in adjuvant therapy, we estimate approximately one quarter of those diagnosed will develop and die from metastatic disease over their lifetimes. Our estimate of life-years lost among this annual cohort is similar to total life-years lost each year in the US from ischemic stroke or opioid use disorders, or hypertensive heart disease. The National Institutes of Health spent $721 million on breast cancer research in 2018, or 1.2% of our estimated societal willingness to pay to prevent discounted quality-adjusted life-years lost to the disease. Citation Format: Stephanie Louise Sansom, Kevin C Ward. Life-years lost to metastatic breast cancer among an annual cohort of women diagnosed with invasive breast cancer in the United States [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-07.