Abstract Introduction: Quality of life (QoL) in oncology captures the well-being of a patient and is considered a significant outcome criterion. Breast cancer (BC) is the most diagnosed cancer in women, however, standardizing integrative therapies to alleviate the burden of cancer and improve QoL is still an unmet need. Art and music therapy might mitigate psychological and emotional distress. We sought to evaluate their efficacy compared to control among patients with BC during or after active therapy. Methods: Seventy-six treated patients with Stages I-III BC were randomly assigned to art, music therapy, or routine oncology care standard of care arm (SOC) for 3 months and received two sessions per month by a licensed therapist (including in-person/virtual and group sessions). The primary outcome was an improvement in QoL measured by the Functional Assessment of Cancer Therapy–Breast (FACT-B) questionnaire and secondary outcomes included: cognitive function measured by Functional Assessment of Cancer Therapy–Cognition (FACT-Cog), response to a 4-component Cleveland Clinic Visual Analog Scale (CCVAS), indicators of anxiety and depression assessed by the Generalized Anxiety Disorder-7 item (GAD-7) and Patient Health Questionnaire-9 item (PHQ-9). All questionnaires were assessed at baseline, 30, 90, and 180 days. Statistical considerations included stratified randomization, and a mean difference in 15 points between either of the interventions. SOC arm was considered relevant at the 3-month mark. Mean improvement within groups was performed using paired t-tests whereas independent t-tests were used to evaluate mean improvement between interventions (1 or 2 vs. SOC arm). All analyses were performed using SPSS version 26 (IBM, Armonk, NY). Results: Forty-five participants completed the study to date and were included in the interim analysis. Median age was 58 (57-59), white race (51.1%), patients on active treatment (45%), art therapy group (n=16), music therapy (n=15) and standard of care (n=14). Significant improvement was noted in the art therapy arm at 3 months in FACT-B physical well-being (p=0.04), functional well-being (p=0.008) domains as well as GAD-7 (p=0.003), PHQ-9 (p=0.04) and FACT-Cog section “impact on quality of life” (p=0.03). At 6 months, the art therapy arm demonstrated lower scores in the CCVAS questionnaire total score, emotional distress (p=0.01) and anxiety (p=0.004) scales. Music therapy participants reported a significant improvement only in GAD-7 index(p=0.04) at 3 and 6 months compared to SOC. No significant difference was found between art and music therapy arms. Conclusion: Art therapy patients exhibited significant improvement in overall QoL (including anxiety, depression, improvement in cognitive function) and 4-scale CCVAS (emotional distress, anxiety, depression, and pain). Music therapy improved anxiety scores (GAD-7). Art and music therapy should be considered in the care of patients to manage cancer associated distress and improve their quality of life. Table 1. Comparison of test changes from 3 months to baseline within groups Table 2. Comparison of test changes from 6 months to baseline within groups Citation Format: Maria Herran, Mohamed Mohanna, Saad Sabbagh, Barbara Dominguez, Kaylee Sarna, Rachel Upton-Rice, Angie Burdine, Zeina Nahleh. A Randomized Controlled Trial to Assess the Benefit of Art & Music Therapy on Quality of Life in Patient with Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-03.