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Symptom burden and reduced quality of life are considerable hurdles in cancer treatment. The Patient-Reported Outcomes Measurement Information System (PROMIS) assesses physical and psychosocial functional status in clinical and research settings. We use PROMIS scores to establish mean symptom burden within a breast cancer patient population, identifying how subgroups compare to one another, examining potential drivers, and characterizing severe symptom burden between subgroups. New cancer patients at the UCSF Breast Care Center (BCC) receive electronic intake questionnaires assessing demographics, health history, and 8 PROMIS domains: depression, anxiety, fatigue, sleep-related impairment and disturbance, cognitive function, applied cognition and physical function. Patients were separated by age and stage of cancer and mean PROMIS reference values for each group were calculated using the NCI's Health Measures scoring system. We computed enrichment of higher levels of anxiety, sleep impairment, fatigue, physical function impairment, and cognitive decline in metastatic patients versus all other cases. Compared to stage 0-III, BCC stage IV patients had lower mean values for all assessed domains (p < 0.05). Within the stage IV population, high levels of anxiety were uniquely predictive of low functional status in 6 out of the other 7 domains. The stage IV population was significantly enriched for severe symptomatology in all domains except sleep-related impairment and disturbance when compared to the stage 0-III population. PROMIS scores indicate that stage IV patients have impaired quality of life in multiple domains. Reference values for demographic groups provide improved guidance in tailoring supportive care referrals. Anxiety emerged as one of the biggest drivers of impairment of other physical, mental, and social functions and thus increased priority addressing anxiety early will likely correspond with improved symptom burden. Our analysis on quality of life will also help determine appropriate thresholds of intervention to trigger referrals and manage a patient's quality-of-life trajectory more systematically. Athena Breast Health Network. Athena Breast Health Network, University of California, San Francisco. All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]