12048 Background: Playing music has been an important part of human culture for millennia. Today more than half of American households have at least one person who plays music, and in the UK 43% of adults play an instrument. Despite the overlap between musicians and people diagnosed with cancer, the effect of cancer treatment on musicianship has not been well-studied. We previously reported that 26% of a musician breast cancer survivor cohort reported difficulty with musicianship after treatment, and here we conduct further analysis to identify treatment and disease factors associated with this difficulty, termed acute musical toxicity (AMT). Methods: The Musical Toxicity Questionnaire was distributed to participants who had previously enrolled in the Mayo Clinic Breast Cancer Registry. PROMIS (Patient-Reported Outcomes Measurement Information System) scores were available through the Registry and treatment details were collected retrospectively. Due to the inter-dependency and high correlation between treatment and disease-related variables, a classification tree analysis (CTA) was performed to identify the combination of variables that most accurately classified patients by AMT. Sixteen variables were analyzed by the algorithm. Logistic regression was utilized for examining associations between AMT and continuous variables. Results: Of the 4075 surveys distributed, 1871 were returned and 535 respondents identified as musicians. Median time from diagnosis was 5.2 years, respondents were mostly stage I or II (71%), and 32% were node positive (N+). Over a quarter (26% or 144 respondents) reported AMT. In the final CTA model, being N+ was strongly associated with AMT (42% of those N+ had AMT, 20% of those not N+ had AMT). For respondents who were N+, those who received endocrine therapy were more likely to have AMT than those who did not (46% vs 21% respectively). Subsequent leaves identified not undergoing axillary lymph node dissection (ALND) and receiving chemotherapy as associated with AMT. For respondents who did not receive chemotherapy, breast reconstruction was associated with AMT (60% vs 19%). Variables such as mastectomy, radiation volume, specific chemotherapies, and stage of disease were not selected by the algorithm. The odds of having AMT decreased by 9.7% and 17% with each additional point in the composite mental health (p=0.003) and physical health (p<0.001) PROMIS scores, respectively. The odds of having AMT increased by 3.5% with each lymph node removed (p=0.001). Conclusions: The final model suggests that the group with the largest proportion of AMT was N+, received endocrine therapy, did not have ALND, and received chemotherapy. Both physical and mental health PROMIS scores were associated with AMT, although the directionality of this relationship requires more study. Care teams should counsel patients on potential musical toxicity and engage in shared decision making with musical patients.