OBJECTIVES/GOALS: Side effects are why up to 50% of women with hormone-positive breast cancer prematurely discontinue aromatase inhibitor (AI) therapy. Pain from altered nociception without clear tissue/nerve damage (nociplastic) is a hypothesized contributing factor to this. Our objective was to evaluate the relationship between nociplastic pain and AI duration. METHODS/STUDY POPULATION: Patients with breast cancer diagnosed between 2012-19 were identified from the University of Michigan Genomics Initiative (MGI). Patients who were female, >65 years old at time of breast cancer diagnosis, and had hormone receptor-positive disease met inclusion criteria. Prior to undergoing surgery, patients completed validated surveys about overall worst pain (Brief Pain Inventory [BPI]), nociplastic pain (2011 Fibromyalgia Survey [FS]), and life satisfaction, with higher scores representing more of the factor. Breast cancer history, treatment, and patient demographics were abstracted from the medical record. Univariate analysis was conducted to evaluate the relationship between age, body-mass index (BMI), chemotherapy, BPI, FS, life satisfaction, and time to discontinuation of initial AI. RESULTS/ANTICIPATED RESULTS: 207 patients were eligible, 133 of whom initiated AI therapy. Of the 133 analyzed patients, mean age was 70.7 years and mean BMI was 30.3. 28 (21%) underwent adjuvant chemotherapy and 79 (59%) received adjuvant radiation prior to initiation of AI therapy. Average nociplastic pain score was 4.0/31 (standard deviation [SD] 4.6), worst pain was 1.5/10 (SD 1.9), and life satisfaction score was 7.3/10 (SD 2.8). The initial AI for 94% of patients (125 patients) was anastrozole. On univariate analysis, only higher nociplastic pain score was statistically associated with premature discontinuation of AI with a HR 1.07 (95%CI 1.00-1.13, p = 0.036). On multivariable analysis, no factors remained statistically significant, although there was a trend for nociplastic pain (HR 1.06, 95%CI 1.00-1.13, p = 0.068). DISCUSSION/SIGNIFICANCE: It is important to identify variables predicting tolerance to therapy so patients can be optimally counseled. Our study suggests that patients with pre-existing baseline pain disorders may be more likely to be nonpersistent with AI therapy. Future study should be conducted to determine if treatments for nocipastic pain improve AI persistence.