Arya, Yajur

7064 Background: Chimeric antigen receptor (CAR) T cell therapy has revolutionized care for relapsed/refractory diffuse large B cell lymphoma (DLBCL), yet granular delineation of real-world immune effector toxicities, organ-specific sequelae and economic burden across demographic and socioeconomic strata requires further exploration. Methods: Using the National Inpatient Sample (2017–2022), we identified adult DLBCL hospitalizations receiving CAR T through ICD-10-PCS codes. Cytokine release syndrome (CRS) [all grades - 2021–2022], immune effector cell–associated neurotoxicity syndrome (ICANS) [all grades – 2022], infections, cardiac events and acute kidney injury (AKI) were identified through ICD-10 codes. Age was stratified into 21-40, 41-60, 61-80 and >81 years. Payer groups were Medicare, Medicaid, Private and Uninsured. Races were White, African American, Hispanic and others [Pacific Islanders, Native Indians, Asians]. Chi-square analysis was performed, and multivariate regression adjusted for demographics, comorbidities, and hospital characteristics. Results: Across >11,000 weighted hospitalizations, inpatient mortality, all-grade CRS and ICANS were comparable across age, race, and payer groups (p>0.05). Inpatient mortality was numerically higher in other minor races (6.6%) vs White (3.3%), African American (3.1%), and Hispanic (0.9%; p=0.230). Any grade CRS was numerically higher in other minor races (72.5%) than in White (62.3%) and African American (60.6%; p=0.614). Any grade ICANS dispersion included 29.5% (White), 39.1% (African American), 22.5% (Hispanic) and 11.1% (Other; p=0.204). A race-specific signal for ICANS grade 5 (p=0.030) was seen, but numbers were small. Among cardiac events, arrhythmias rose from 7.6% (age 21–40 years) to 57.1% ( age ≥81 years) (p<0.001). By payer, arrhythmias were highest in Medicare (31.2%; p<0.001). Other cardiac events including myocardial infarction, stroke and cardiogenic shock were similar across groups. Pneumonia rates varied by payer, peaking in the Uninsured (23.8%; p=0.010). Sepsis and septic shock rates showed no differences. AKI (p=0.007) rates showed differences but attenuated after adjustment. Hispanic and other minor races had lower adjusted costs than White (Odds ratio [OR] 0.9, p=0.046; OR 0.8, p=0.006), while ages 61–80 had higher adjusted costs vs 21–40 (OR 1.2, p=0.023). Conclusions: In this national cohort, CRS, ICANS and mortality were similar across demographic and payer strata, indicating consistent immune effector safety. Cardiac arrhythmia rates were higher among the elderly and Medicare beneficiaries. There were lower expenditures among minor race groups and higher costs in elderly. These findings highlight discrete domains of variability and suggest intensified cardiac surveillance in elderly and equitable resource allocation to optimize outcomes with CAR-T.

5543 Background: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Endometrial cancer is the most common gynecologic malignancy, and obesity represents a well-established, modifiable risk factor that may adversely affect oncologic outcomes through chronic inflammation and metabolic dysregulation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with endometrial cancer and comorbid obesity. Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network, covering January 2000 to December 2025, encompassing data from 168 global healthcare organizations. Patients aged 18 and above with endometrial cancer and comorbid obesity were identified and then stratified into two groups based on treatment with GLP1 agonists or not. The two groups were then propensity-matched based on age, ethnicity, medical comorbidities, and stage of cancer. Outcomes were assessed for five years from treatment initiation and included overall mortality, myocardial infarction (MI), ischemic stroke; development of peritoneal, lymph node, and visceral metastases; sepsis, pancreatitis, and ED visits. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: After propensity matching, 6352 patients were included in each cohort with balanced baseline characteristics. Our analysis found that patients with endometrial cancer and comorbid obesity who received GLP-1 agonists had a significantly lower risk of overall mortality (Hazard Ratio [HR]: 0.45, 95% CI: 0.39-0.51, p-value <0.001), development of peritoneal metastases (Risk Difference [RD]: -2.16%, 95% CI: -2.74% to -1.58%, p-value <0.001), nodal metastases (RD: -0.41%, 95% CI: -0.72% to -0.09%, p-value =0.01), visceral metastases (RD: -3.76%, 95% CI: -4.60% to -2.93%, p-value =0.01), and sepsis with and without shock (RD: -1.42%, 95% CI: -2.14% to -0.70%, p-value <0.001) compared to patients who did not receive GLP-1 agonists. There was no statistically significant difference in the rates of MI, ischemic stroke, ED visits, and pancreatitis between the two cohorts. Conclusions: In this large real-world analysis, patients with endometrial cancer and comorbid obesity who received GLP-1 agonists had lower rates of overall mortality; peritoneal, lymph node, and visceral metastases, and sepsis with or without shock. Additional longitudinal cohort studies are imperative to explore the associations between these agents and inform clinical practice guidelines in this patient population.

1615 Background: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment but cause adverse events, including immune-related colitis (ir-colitis). Accurate identification of ir-colitis is critical for improving patient outcomes and clinical research. However, current methods relying on ICD codes have substantial limitations: non-specific categories that fail to capture the cases or distinguish cases from infectious or ischemic etiologies, as well as incomplete coding that leads to missed cases. Large language models (LLMs), with advanced natural language understanding capabilities, offer a scalable approach for automated phenotyping using unstructured clinical notes. We aimed to develop and evaluate an LLM-based approach for identifying ir-colitis in patients with lung cancer receiving ICIs and compare it with ICD code based method. Methods: We identified 5,278 lung cancer patients with ICI administration at Mayo Clinic (2012-2025). To investigate ir-colitis occurrence within two years after ICI initiation, patients were stratified into three ICD-based cohorts: (1) IR-Colitis, with clinician-assigned ir-colitis-specific diagnosis codes; (2) Non-IR Colitis, with colitis diagnosis codes excluding ir-colitis; and (3) No-Colitis, absent of any colitis-related codes. We used three open-source LLMs to process clinical notes : Llama4, MedGemma, and Qwen. Prompts were designed to extract both gold standard evidence (explicit ir-colitis terminology, such as "immune-mediated colitis" and "checkpoint inhibitor colitis") and supportive evidence (such as pathology and lab results). Results: Llama4 demonstrated superior accuracy among three LLMs in manual evaluation and was thus selected for all cohort analyses. Among ICD-based IR-Colitis patients (n = 339), 82.0% had confirmatory evidence while 18% lacked evidence, suggesting potential false-positive coding. In the Non-IR Colitis cohort (n = 297), LLM-based extraction identified 43.8% patients in fact had ir-colitis, demonstrating substantial misclassification. In the No-colitis cohort (n = 4,642, random sample of 996 for analysis), the LLM identified 10.7% with documented ir-colitis, revealing substantial missing by administrative coding. Conclusions: LLM-based phenotyping demonstrates superior sensitivity for identifying ir-colitis compared to ICD codes alone, successfully uncovering cases missed by administrative coding. This scalable approach enables more comprehensive case identification for immunotherapy safety research and clinical surveillance. ICD-Based Cohorts LLM-Identified ir-Colitis Gold Standard Evidence Supportive Evidence Any Evidence ir-Colitis (n = 339) 277/339 (81.7%) 275/339 (81.1%) 278/339 (82.0%) Non-ir-Colitis (n = 297) 129/297 (43.4%) 126/297 (42.4%) 130/297 (43.8%) No Colitis (n = 996) 106/996 (10.6%) 104/996 (10.4%) 107/996 (10.7%)

10522 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality. While antiviral and metabolic therapies have reduced incidence, scalable pharmacologic strategies for primary prevention (PP) remain a critical unmet need. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated preclinical antitumor activity and the potential to mitigate hepatic lipotoxicity while promoting metabolic reprogramming to stabilize cirrhosis. However, while chemoprevention signals are observed in metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, the efficacy of GLP-1RAs for PP across diverse liver disease etiologies remains underexplored. To address this gap, we conducted a global, multicenter analysis on the efficacy and safety of GLP-1RAs for the PP of HCC in a pan-etiology high-risk cohort. Methods: A retrospective cohort study was conducted using the TriNetX database (150M patients across 108 health organizations). Adults 18–90 years at elevated HCC risk with ≥ 1 risk factor (chronic viral hepatitis, cirrhosis, MASLD, alcohol use disorder, or hereditary liver disorders) were identified. Cohort A (≥3 months of GLP-1RA) was propensity score-matched 1:1 with Cohort B (non-users) on demographics, HbA1c, BMI, and MELD-Na scores. The primary endpoint was incident HCC, and secondary endpoints were incidence of gastrointestinal (GI) side effects. We employed a 3-month lag period to mitigate immortal time bias. Time-to-event outcomes were assessed via Kaplan-Meier analysis and Cox proportional hazards models. Sensitivity & subgroup analyses were performed to confirm robustness across non-metabolic etiologies. Results: After matching, 592,718 patients were analyzed (296,359 per cohort). Median follow-up was 2,450 days for GLP-1RA users vs 2,114 days for non-users. GLP-1RA use was associated with a 73% reduction in incident HCC (140/296,345 events vs 432/296,198) [HR 0.271 (0.224-0.328)], (NNT=1,015). Notably, the protective effect was most pronounced in non-diabetics [HR 0.179 (0.140-0.229)] and lean patients (BMI < 29) [HR 0.161 (0.103-0.252)]. Risk reductions were sustained across all etiologies, including alcohol liver disease (HR 0.379), cirrhosis (HR 0.456), chronic viral hepatitis (HR 0.477), and MASLD (HR 0.605). GLP-1RA use was associated with a significant increase in GI adverse events. Conclusions: GLP-1RA use was associated with a 73% reduction in incident HCC, consistent across subgroups. The enhanced benefit in non-diabetic and lean cohorts suggests a direct anti-neoplastic mechanism independent of weight loss or glycemic control. The NNT of 1,015 highlights the substantial public health impact of GLP-1RA therapy in preventing a high-mortality malignancy. These findings warrant prospective validation.

10520 Background: Therapeutic options for breast cancer (BC) prevention for high-risk women remain limited, and not all eligible patients opt for endocrine therapy due to concerns related to adverse events (AEs). GLP1RAs are widely used for obesity and type 2 diabetes mellitus; their role in BC primary prevention (PP) in high-risk women with obesity has not been evaluated. Methods: Using the TriNetX Global Network (150 million patients, 108 organizations), we analyzed de-identified records of high-risk women aged 18–90 years with a BMI ≥ 30 who had health care encounters between January 1, 2000, and January 1, 2025, identified via ICD-10 codes. High risk was defined as at least one of the following: genetic predisposition to BC, family history of BC, atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, or dense breasts. Patients were grouped as having GLP1-RA use or no GLP-1RA use. Patients with a prior history of BC or use of endocrine therapy were excluded. GLP-1RA users were propensity score-matched 1:1 with non-users based on demographics, comorbidities, social determinants of health, lifestyle factors, BMI, HbA1c, and prior breast imaging. Incident BC served as the primary endpoint, with key AEs as secondary measures. Kaplan–Meier analysis and Cox proportional hazards models were utilized to assess outcomes, which were further validated through subgroup and sensitivity analyses. Results: Among 80,480 high-risk women with a BMI ≥ 30, 46,581 were assigned to each cohort. Baseline demographics were balanced between cohorts (mean age: 46 years, 70% White, 21% Black). Median follow-up was 2,790 vs 2,630 days for GLP-1RA users and non-users, respectively. BC incidence was 2.95% in GLP-1RA users (1,164/39,495 cases) vs 3.01% in non-users (1,200/39,057 cases) (3.27 vs. 3.57 cases per 1,000 person-years; HR 0.844; 95% CI, 0.779–0.915). GLP-1RA users exhibited an increased risk of endometrial cancer (HR 1.273; 95% CI, 1.088–1.491) and osteoporosis (HR 1.124; 95% CI, 1.054–1.199). No significant association was observed for venous thromboembolism. Gastrointestinal AEs were significantly higher in the GLP-1RA cohort. Conclusions: GLP-1RA use was associated with a modest reduction in BC incidence among high-risk women with obesity in this real-world study. Prospective randomized trials are needed to validate these associations.

10507 Background: Despite advances in understanding leukemogenesis, no validated primary prevention strategies exist. Obesity is a dose-dependent risk factor for leukemia. Emerging data implicate epigenetic regulators, specifically the histone methyltransferase GLP (EHMT1), as a driver of leukemic survival; its inhibition induces cell death in CLL and promotes differentiation in AML. We present the first real-world analysis evaluating GLP-1 receptor agonists (GLP-1RA) for the primary prevention of leukemia in high-risk populations. Methods: Using the TriNetX global research network (150 million patients across 108 healthcare organizations), we identified adults at elevated leukemia risk based on ≥1 factor (prior chemo/radiation, MDS, MPN, family history, genetic syndromes, tobacco use, or BMI ≥30). Patients with ≥2 months of GLP-1RA use were propensity-matched 1:1 to non-users by demographics, comorbidities, and prior chemotherapy. The primary endpoint was the incidence of ALL, AML, CLL, or CML; secondary endpoints were adverse events related to GLP-1RA. Individuals with pre-existing leukemia were excluded. Cox proportional hazards models and sensitivity analyses were used to assess associations. Sensitivity and subgroup analysis confirmed robustness. Results: Of 426,670 high-risk individuals, 213,335 were matched to each cohort; standardized mean differences were <0.1 for all covariates. Across >1.2 million person-years of follow-up, GLP-1RA use was associated with a 63% risk reduction in incident AML (47/213,300 vs 75/213,261; HR 0.37, 95% CI 0.26–0.53; p < 0.001) and a 50% reduction in ALL (42/213,304 vs 53/213,277; HR 0.50, 95% CI 0.33–0.75; p = 0.001). The protective effect for AML remained significant when restricted to patients with prior chemotherapy exposure and was independent of baseline BMI. No significant reductions were observed for CML or CLL. While GI adverse events were higher in the GLP-1RA cohort, the protective signal was consistent across age and ethnic subgroups. Conclusions: This is the first large-scale study to demonstrate a significant reduction in incident AML and ALL using GLP-1 receptor agonists in high-risk patients. By linking clinical metabolic intervention to the EHMT1 epigenetic pathway, these findings provide a novel, scalable pharmacologic strategy for the primary prevention of acute leukemias, potentially transforming the management of high-risk and obese populations.

712 Background: Bladder cancer is one of the most common malignancies of the urinary tract. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Their pleiotropic benefits including improved insulin sensitivity, potential anti-proliferative and anti- inflammatory benefits may significantly benefit these patients by potentially influencing tumor biology. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with bladder carcinoma with comorbid obesity, exploring potential interactions between metabolic modulation and disease behaviour. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with bladder cancer and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, sex, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, heart failure, chronic kidney disease (CKD), ischemic stroke, risk of metabolic dysfunction associated liver disease and need for hemodialysis. Results: We identified 1282 patients with bladder cancer and obesity who received GLP-1 receptor agonists, and 10238 patients with bladder cancer and obesity who did not receive GLP-1 therapy. The average age was 67.3 years in the first cohort and 69 years in the second cohort. After propensity matching, each cohort consisted of 1282 patients with similar baseline characteristics and ethnicity distribution. Our analysis found that over 5 years, patients with bladder cancer and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.611, 95% CI: 0.515 to 0.725, p-value =0.04), myocardial infarction (Risk difference: -4.418%, 95% CI: -6.608% to -2.228%, p-value <0.001), heart failure (Risk difference: -5.226%, 95% CI: -8.883% to -1.569%, p-value =0.005), CKD (Risk difference: -7.193%, 95% CI: -10.675% to -3.711%, p-value <0.001). There was no statistically significant difference in the risk of metabolic dysfunction associated liver disease and need for hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with bladder cancer and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, heart failure and CKD. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.

484 Background: Renal cell carcinoma (RCC) is the most common type of urogenital cancer. Lifestyle and metabolic risk factors seem to play an important role in this rising incidence. Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for the treatment of type 2 diabetes and obesity. Emerging evidence suggests that these agents may have potential anti-tumor activity as GLP-1 signaling may influence pathways involved in cell proliferation and inflammation. Our study aims to evaluate the impact of GLP-1 receptor agonists on outcomes among patients with RCC and comorbid obesity. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Adult patients aged 18 and above with RCC and comorbid obesity were identified and then stratified into two groups based on treatment with GLP-1 agonists or not. The two groups were then propensity-matched based on age, race, and common comorbidities. We followed these patients for 5 years to assess outcomes, including overall mortality, myocardial infarction, heart failure, ischemic stroke, chronic kidney disease (CKD), metabolic dysfunction-associated steatotic liver disease (MASLD), and need for hemodialysis. Results: We identified 2232 patients with RCC and obesity who received GLP-1 receptor agonists, and 13090 patients with RCC and obesity who did not receive GLP-1 therapy. After propensity matching, each cohort consisted of 2231 patients with similar baseline characteristics. Our analysis found that over 5 years, patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of overall mortality (Hazard Ratio (HR): 0.493, 95% CI: 0.427 to 0.57, p-value < 0.001), myocardial infarction (Risk Difference: -2.239%, 95% CI: -3.836 to -0.642, p-value = 0.006), heart failure (Risk Difference: -4.213%, 95% CI: -6.876 to -1.551, p-value = 0.002), ischemic stroke (ischemic stroke: -2.111%, 95% CI: -3.44 to -0.781, p-value = 0.002), and CKD (Risk Difference: -8.526%, 95% CI: -11.441 to -5.611, p-value < 0.001). There was no statistically significant difference in the risk for MASLD and need for hemodialysis between the two subgroups. Conclusions: Our study revealed that patients with RCC and obesity who received GLP-1 receptor agonists had a significantly lower risk of mortality, myocardial infarction, heart failure, CKD and ischemic stroke. Further longitudinal cohort studies are imperative to better understand these associations and guide evidence-based clinical practice in this population.

Abstract Introduction: Breast cancer most commonly metastasizes to the bones, with bone pain and other skeletal related events (SREs) having a limiting effect on quality of life. Bisphosphonates are widely used in breast cancer patients to reduce SREs and bone loss, particularly in those with bone metastases or receiving endocrine therapy. We aim to study the real world comparative data between two widely used bisphosphonates in clinical practice, zoledronic acid and pamidronate, along with evaluation of their toxicity profiles. Methods: A retrospective cohort study was conducted using the US Collaborative Network TriNetX, covering January 2000 to December 2023, and encompassing data from 105 global healthcare organizations. Female patients aged 18 and above with breast cancer metastatic to the bone were identified and then stratified into two groups based on treatment with zoledronic acid or pamidronate. The two groups were then propensity-matched based on age, sex, race, and comorbidities. We followed these patients for 5 years to assess outcomes, including mortality, osteoporotic fracture, hypercalcemia, pathological fracture, fall, and osteonecrosis. Results: We identified 7887 patients in the zoledronic acid cohort and 635 patients in the pamidronate cohort. After propensity matching, each cohort consisted of 625 patients with similar baseline characteristics. The average age was 66.4 years in zoledronic acid cohort and 69.1 in the pamidronate cohort. In the zoledronic acid cohort, the ethnicity distribution was 74.68 % White, 11.55% African American, and 6.36% Hispanic. In contrast, the pamidronate group had an ethnicity distribution of 63.04% White, 20.64% African American, and 8.16% Hispanic. Our analysis found that within 5 years, patients with breast cancer metastatic to the bone who received zoledronic acid had a significantly lower risk of mortality (Hazard Ratio [HR] 0.593, 95% CI: 0.509-0.691, p-value &lt;0.001), osteoporotic fracture (Risk difference: -5.28%, 95% CI: -7.65 to -2.90), p-value &lt; 0.001), hypercalcemia [HR: 0.262, 95% CI: 0.212 - 0.323, p-value = 0.001), pathological fracture (Risk difference: -6.88%, 95% CI: -10.69 to -3.07), p-value &lt; 0.001). However, the zoledronic acid group had higher risk of falls [Risk difference: 3.52%, 95% CI: 0.518 to 6.522), p-value = 0.021). There was no statistically significant difference in the occurrence of osteonecrosis between the two cohorts. Conclusion: Our study revealed that patients with breast cancer with metastatic disease to the bone who received zoledronic acid had significantly lower rates of mortality, osteoporotic fracture, hypercalcemia, and pathological fracture compared to those receiving pamidronate. Additional longitudinal cohort studies are imperative to explore the outcomes between these agents and inform clinical practice guidelines. Citation Format: Y. Arya, A. Syal, C. Jones, H. Mahadevia, N. Batra, A. Uriepero-Palma. Real-world outcomes comparing zoledronic acid and pamidronate in patients with metastatic breast cancer with bone metastases: A propensity score matched analysis from a global federated health research network [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-06-02.

Abstract Introduction: Patients with metastatic breast cancer frequently develop bone metastases and experience other skeletal-related events (SREs). These complications substantially impair quality of life and may negatively influence clinical outcomes. In this context, bisphosphonates and denosumab are the most commonly utilized therapeutic agents. We aim to study the real-world comparative data between bisphosphonates and denosumab in breast cancer patients with bony metastases along with evaluation of their toxicity profiles. Methods: A retrospective cohort study was conducted using the US Collaborative Network, TriNetX, covering January 2000 to December 2023, encompassing data from 105 global healthcare organizations. Female patients aged 18 and above with breast cancer metastatic to the bone were identified and then stratified into two groups based on treatment with zoledronic acid or pamidronate. The two groups were then propensity-matched based on age, sex, race, and comorbidities. We followed these patients for 5 years to assess outcomes, including mortality, osteoporotic fracture, hypercalcemia, pathological fracture, fall, and osteonecrosis. Results: We identified 7887 patients in the zoledronic acid cohort and 635 patients in the pamidronate cohort. After propensity matching, each cohort consisted of 625 patients with similar baseline characteristics. The average age was 66.4 years in the zoledronic acid cohort and 68.5 in the denosumab cohort. In the zoledronic acid cohort, the ethnicity distribution was 74.68 % White, 6.36% Hispanic, and 11.55% African American. In comparison, the denosumab group had an ethnicity distribution of 74.49% White, 10.31% African American, and 5.68% Hispanic. Our analysis found that within 5 years, patients with breast cancer metastatic to the bone who received zoledronic acid had a significantly lower risk of mortality (Risk difference: -3.49%, 95% Confidence Interval [CI]: -5.063 to -1.916), p-value &lt;0.001) compared to denosumab. However, patients in the zoledronic acid arm were noted to have a higher risk of osteoporotic fracture (Risk difference: 0.817%, 95% CI: 0.232 to 1.402), p-value = 0.006), hypercalcemia [Hazard Ratio [HR]: 1.524, 95% CI: 1.407 to 1.65, p-value &lt;0.001), and pathological fracture (HR: 1.501, 95% CI: 1.349 to 1.671), p-value =0.03). There was no significant difference in the occurrence of falls and osteonecrosis between the two subgroups. Conclusion: Our study revealed that patients with breast cancer with metastatic disease to the bone who received zoledronic acid had significantly lower rates of mortality but higher occurrence of osteoporotic fracture, hypercalcemia, and pathological fracture compared to those receiving denosumab. Additional longitudinal cohort studies are imperative to explore the outcomes between these agents and inform clinical practice guidelines in these patients. Citation Format: A. Syal, Y. Arya, C. Jones, H. Mahadevia, N. Batra, A. Uriepero Palma. Real-world outcomes comparing zoledronic acid and denosumab in patients with metastatic breast cancer and bone metastases: A propensity score matched analysis from a global federated health research network [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-17.