Poster Spotlight 8: Beyond the Scale—Obesity and GLP-1 Therapies in Breast Cancer

C. Cao¹, K. Ballman², L. McCall³, C. Alfano⁴, V. Bernstein⁵, T. Crane⁶, L. Delahanty⁷, L. Frank¹, P. Goodwin⁸, O. Hahn⁹, D. Hershman¹⁰, J. Hopkins¹¹, M. Irwin¹², E. Mayer¹, L. Minasian¹³, L. Nebeling¹⁴, M. Neuhouser¹⁵, E. Paskett¹⁶, P. Spears¹⁷, V. Stearns¹⁸, C. Thomson¹⁹, T. Wadden²⁰, A. Weiss²¹, J. White²², C. Hudis²³, E. Winer²⁴, A. Partridge¹, L. Carey²⁵, J. Ligibel¹; ¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, ³Alliance Statistics and Data Management Center, Duke University, Durham, NC, ⁴Cancer Institute, Northwell Health, New Hyde Park, NY, ⁵Department of Medical Oncology, BC Cancer/University of British Columbia, Vancouver, BC, CANADA, ⁶Division of Medical Oncology, Miller School of Medicine, University of Miami, Miami, FL, ⁷Diabetes Research Center, Massachusetts General Hospital, Boston, MA, ⁸Department of Medical Oncology, Sinai Health/Lunenfeld-Tananbaum Research Institute, University of Toronto, Toronto, ON, CANADA, ⁹Department of Medical Oncology, UChicago Medicine Comprehensive Cancer Center, Chicago, IL, ¹⁰Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, New York, NY, ¹¹Department of Medical Oncology, SCOR NCORP/Novant Health Cancer Institute, Kernersville, NC, ¹²Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, ¹³Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, ¹⁴Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, ¹⁵Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, ¹⁶Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, ¹⁷Office of Community of Outreach and Engagement, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, ¹⁸Department of Medicine, Weill Cornell Medical Center, New York, NY, ¹⁹Health Promotion Sciences, College of Public Health, University of Arizona, Tucson, AZ, ²⁰Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, ²¹Department of Surgery, University of Rochester, Rochester, NY, ²²Department of Radiation Oncology, Kansas University Medical Center, Kansas City, KS, ²³Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ²⁴Department of Medical Oncology, Yale Cancer Center, New Haven, CT, ²⁵Department of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, NC.

Background: Obesity is a poor prognostic factor in early breast cancer (BC). The BWEL trial (Alliance A011401; NCT02750826) is a phase 3 randomized trial testing the impact of a weight loss intervention (WLI) on invasive disease-free survival in women with stage II-III BC and a body mass index (BMI) ≥27 kg/m². Here we report trajectories of weight change in BWEL WLI participants (pts). Methods: Eligible pts were within 16 months of diagnosis of stage II-III HER2-negative BC, had completed chemotherapy (chemo) and radiation (if given), and were randomized 1:1 to a telephone-based WLI, focused on caloric restriction and exercise, plus health education (HE) or to an HE-alone control group. WLI pts were assigned a trained coach at the BWEL call center and received 42 phone calls over the 2-year (yr) WLI period. Weight and height at baseline, 6 and 24 months were collected by study staff. All WLI pts were provided with a Fitbit wireless scale. Fitbit weight records (FWRs) were automatically imported to the BWEL portal for pts with wireless access and self-reported in the portal for pts without wireless access. FWRs were averaged (avg) by week (wk) from the WLI start date up to 104 wks. Baseline pt factors were self-reported; treatment history was abstracted from the medical record. Linear mixed-effect models were used to evaluate trajectories of weight change over the 104-wk WLI. Principal component analysis and multinomial models were used to examine distinct clusters of weight trajectories. Results: 3180 pts were enrolled from 637 sites between 8/2016 and 2/2021. FWRs were available from 1508 of 1591 WLI pts, with a total of 366,294 FWRs collected during the 2-yr WLI period. In pts with FWRs, mean baseline BMI was 34.4 ± 5.6 kg/m², mean age was 53.2 ± 10.3 yrs, 10.8% self-identified as Non-Hispanic (NH) Black and 6.1% as Hispanic, 81.1% received chemo and 56.9% were postmenopausal. No statistically significant differences in baseline factors were observed between pts with and without FWRs. Intraclass correlation coefficient of baseline weights collected by study staff and by Fitbit scales was 0.99. In the WLI cohort, avg weekly weight (kg) decreased from 91.4 (95% CI: 90.6-92.3) at baseline to 85.6 (95% CI: 84.8-86.5) by wk 40, corresponding to a peak loss of 6.1% (95% CI: 5.7-6.4) of baseline weight. Weight remained stable until wk 52 and then gradually increased to 87.0 kg (95% CI: 86.2-87.9) at wk 104, corresponding to a 4.4% (95% CI: 4.0-4.8) loss at wk 104 vs. baseline. Principal component analysis identified 3 distinct weight trajectories: 67.6% of pts experienced peak weight loss of 6.6% (95% CI: 6.3-6.9) of baseline weight, 10.0% experienced peak loss of 17.5% (95% CI: 16.8-18.2) of baseline weight, and 22.4% did not achieve weight loss, gaining on avg 2.2% (95% CI: 1.7-2.6) of baseline weight. Pts with college (relative risk ratio [RRR]=1.41, 95% CI: 1.03-1.92) and post-graduate education (RRR= 1.58, 95% CI: 1.13-2.20) and those who were premenopausal (RRR=1.70, 95% CI: 1.28-2.26) were more likely to be in the cluster that did not lose weight. Pts who were NH White (RRR=3.60, 95% CI: 1.95-6.68), postmenopausal (RRR=1.94, 95% CI: 1.28-2.95), had no alcohol use (RRR=1.49, 95% CI: 1.03-2.16), had not received chemo (RRR=1.76, 95% CI: 1.15-2.72), and had <3 chronic conditions (RRR: 2.12, 95% CI: 1.23-3.66) were more likely to be in the cluster with the highest weight loss. Conclusion: Longitudinal weight data from BWEL demonstrate peak weight loss of 6.1% in the WLI cohort at 40 wks, with distinct trajectories indicating differential responses to the WLI. This work demonstrates the feasibility of using digital health tools to track outcomes in the setting of a large-scale weight loss intervention study and informs future precision behavioral interventions in oncology. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180863. https://acknowledgments.alliancefound.org.

T. Adamson¹, N. E. Gharaibeh¹, R. Shaw¹, C. D. Morrissey¹, S. Kapoor¹, A. Podolski¹, E. Teplinsky²; ¹Medicine, Valley Health System, Paramus, NJ, ²Medicine, Valley Health System, New Jersey, NJ.

Introduction: Estrogen plays a critical role in regulating metabolism, body composition and glucose homeostasis. Its decline after menopause increases the risk of metabolic disorders, including type 2 diabetes & obesity. Endocrine therapies (ET), including tamoxifen and aromatase inhibitors (AI), effectively reduce recurrence & improve survival in women with hormone receptor-positive (HR+) breast cancer (BC), but may disrupt metabolic health, contributing to increased insulin resistance & weight gain. The use of pharmacologic weight loss agents, particularly GLP-1 receptor agonists (GLP-1 RAs) is steadily increasing. Data on their efficacy in patients with BC on ET remains limited. This retrospective study evaluated total body weight loss in patients with stage 0-IV HR+ BC receiving both ET and weight loss medications. Methods: A retrospective chart review was conducted of approximately 110 patients (pts) with HR+ BC diagnosis evaluated at our institution’s weight management center. Of these, 24 pts met inclusion criteria: stage 0-IV HR+ BC, initiation of ET ≥ three months prior to starting weight loss medications, and ≥ 2 follow-up visits for weight management. Data collected included demographics, BC history, comorbidities, and weight loss medication use and body weights. The primary objective was to evaluate the mean total body weight loss at 3 months (mo), 6 mo, 9 mo and 12 mo, when available. Categorical variables were summarized using percentages. Changes in weight from baseline to each follow-up were analyzed using paired t-tests. A repeated measures analysis was performed for patients with data across all timepoints. Results: Median age was 61.5 years (range 43-73); BC stage 0 (n=1); stage 1 (n =18); stage 2 (n =3); stage 3 (n =1); stage 4 (n =1). One pt had HR+/HER2+ BC; remainder were HER2-negative. All were postmenopausal: 2 were on a GNRH agonist and 5 had prior surgical menopause. ET at weight loss medication initiation: anastrozole (n=17); exemestane (n=3), letrozole (n=2), fulvestrant (n=1); tamoxifen (n=1). Median time on endocrine therapy when starting weight loss medications: 41.5 mo (range 5-107). Common comorbidities: pre-diabetes (29.2%), type II diabetes (16.7%), and hyperlipidemia (70.8%). 8.3% had prior bariatric surgery. Most pts (83.3%,n=20) were prescribed GLP-1 RAs and 16.7% (n=4) phentermine. The GLP-1s used were Zepbound (n=10); Mounjaro (n=5); Wegovy (n=4); Ozempic (n=2); Saxenda (n=2); Victoza (n=1); some pts switched agents during treatment. Median initial weight at time of starting weight loss medications was 192.7 lbs (range 153.9-273). All patients had a baseline and 3 mo follow-up visit, with a mean weight loss of 18.8 lbs between timepoints (p<0.001). At 6 mo, 23 patients had available data, showing a mean reduction of 30.9 lbs (p<0.001) from baseline. At nine and twelve mo, follow-up data were available for 50% of patients (n=12), with mean weight losses of 39.6 lbs (p=0.033) and 37.9 lbs (p=0.004), respectively. Among the 8 patients with complete data, repeated measures analysis demonstrated a significant weight reduction from an average of 211.7 lbs to 178.9 lbs (p<0.001). No new safety concerns were identified. Conclusion: The use of GLP-1 RAs or phentermine in this cohort of patients with HR+ BC on ET was associated with meaningful weight loss, most notably within the first nine months, with weight plateauing thereafter. The degree of weight loss observed was comparable to outcomes reported in the general population using these medications. Limitations include a small sample size and grouping of all weight loss agents together. Updated data with a larger sample size and body composition analysis, will be presented. Prospective studies are warranted to further assess long-term efficacy in this pt population.

P. Saha¹, O. Israel², C. Sanchez³, L. Eldridge⁴, K. Kuchta⁵, K. A. Yao⁵; ¹Oncology, Endeavor Health, Chicago, IL, ²Medicine, University of Michigan, Ann Arbor, MI, ³Medicine, Endeavor Health, Evanston, IL, ⁴Research Institute, Endeavor Health, Evanston, IL, ⁵Surgery, Endeavor Health, Evanston, IL.

Impact of Obesity in Premenopausal Women with Early-Stage HR+/HER2- Breast Cancer Treated With Adjuvant Endocrine Therapy Poornima Saha, MD, Ori Israel, Courtney Sanchez, MD PhD, Laura Eldridge, MS, Kristine Kuchta, MS, Katharine A. Yao, MD, MS Background:Hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor 2 negative (HER2–) breast cancer is the most common subtype of breast cancer and is primarily treated with endocrine therapy (ET), including tamoxifen (tam) alone or ovarian function suppression (OFS) with tam or aromatase inhibitors (AI). Body mass index (BMI) can influence the effectiveness of ET; however, the impact of BMI on outcomes in premenopausal women remains unclear. Previous studies in postmenopausal women have shown worse outcomes among obese women receiving ET. Given the rise in obesity and limited literature focused on premenopausal patients, it is essential to gain a better understanding of how BMI affects ET outcomes. Methods:We analyzed the medical records of premenopausal women (defined as age < 50) with Stage 1-3 HR+/HER2– breast cancer from January 2012 to December 2023. We collected demographic, clinicopathologic characteristics, and treatment information. Patients with non-invasive breast cancer, those who did not begin ET, and those who received an AI alone were excluded. We examined recurrence and survival outcomes by BMI and ET type, controlling for age, tumor grade, and stage. Results:723 women with Stage 1-3 HR+/HER2- breast cancer treated with ET were identified. Of these, 345 were characterized as normal weight (BMI ≤ 24.9), 210 were overweight (BMI 25.0-29.9), and 168 were obese/severely obese (BMI ≥ 30.0). There was a significant difference in BMI among racial groups, with Black and Hispanic patients diagnosed with breast cancer being more likely to be obese/severely obese than White or Asian/Pacific Islander (API) women. Women with higher BMIs were also more likely to be diagnosed with larger tumors (≥ 3.0 cm), but there was no significant interaction between BMI and clinical stage, node positivity, or grade. Of the 723 total patients treated with ET, 185 (25.6%) received OFS with either Tam or an AI. 538 (74.4%) of patients were treated with Tam alone. Multivariable analysis controlling for age, grade, and stage did not show that increasing BMI was associated with Tam alone use (OR 0.99 (0.96-1.01), p=0.2997). At a median follow-up of 66 months, 64 patients were found to have a breast cancer recurrence: 32 recurrences occurred in women with normal weight, 17 recurrences occurred in those who were overweight, and 15 recurrences occurred in those who were obese/severely obese. 5-year survival rates were 94.6% in the obese/severely obese group; 95.1% in the overweight group and 98.1% in the normal weight group (p=0.7027). Conclusions In contrast to currently reported data in postmenopausal women, we did not find that premenopausal women with early-stage HR+/HER2– breast cancer and higher BMIs were at increased risk of recurrence or worse survival but longer term follow up is needed.

E. Obomanu¹, C. Jones², A. Ratnani¹, C. Ugwu¹, M. Megiso¹, T. Verinumbe¹, S. King¹, A. Ramkissoon³, C. Dourado⁴; ¹Internal Medicine, Jefferson-Eintein Hospital, Philadelphia, PA, ²Hematology-Oncology, University of Texas, San Antonio, San Antonio, TX, ³Paediatrics, Joe Dimmagio Children’s Hospital, Florida, FL, ⁴Hematology-Oncology, Jefferson-Eintein Hospital, Philadelphia, PA.

INTRODUCTIONChemotherapy-induced side effects account for over 25% of cancer-related morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), approved for diabetes management and weight loss, may also ameliorate treatment toxicity. This retrospective analysis evaluates whether concurrent GLP-1 RA use during chemotherapy in breast cancer(BC) patients improves tolerability, reduces complication rates, and enhances overall well-being, with the goal of informing novel supportive-care protocols. METHODSWe queried the Global Collaborative Network using ICD-10 codes to identify BC patients treated with one or more of the following agents: doxorubicin, cyclophosphamide, paclitaxel, docetaxel, carboplatin, capecitabine, or gemcitabine. Patients receiving chemotherapy plus a GLP-1 RA were assigned to Cohort A (n = 5,685), and those on chemotherapy alone to Cohort B (n = 5,685). Propensity score matching adjusted for demographic and clinical confounders. The primary endpoint was the incidence of chemotherapy-related side effects and complications. Associations between GLP-1 RA use and adverse events were estimated via multivariate logistic regression. RESULTSBoth cohorts comprised 5,685 patients; Cohort A had a mean age of 62 years (62.2% White, 18.6% Black, 9.5% Hispanic; 96% female; BMI 35.3 ± 7.5), and Cohort B a mean age of 63 years (62.7% White, 18.5% Black, 8.9% Hispanic; 96% female; BMI 29.3 ± 7.1). Adjusted analyses demonstrated that GLP-1 RA use was associated with significantly lower risks of anemia (RR 0.617, 95% CI 0.57-0.667; p < 0.0001), neutropenia (RR 0.478, 95% CI 0.429-0.532; p < 0.0001), thrombocytopenia (RR 0.587, 95% CI 0.514-0.671; p < 0.0001), sepsis (RR 0.679, 95% CI 0.599-0.769; p < 0.0001), nausea and vomiting (RR 0.711, 95% CI 0.656-0.772; p < 0.0001), diarrhea (RR 0.763, 95% CI 0.699-0.834; p < 0.0001), venous thromboembolism (RR 0.592, 95% CI 0.5-0.701; p < 0.0001), mucositis (RR 0.440, 95% CI 0.374-0.519; p < 0.0001), fatigue (RR 0.755, 95% CI 0.684-0.834; p < 0.0001), hot flashes (RR 0.610, 95% CI 0.531-0.699; p < 0.0001), myalgia/arthralgia (RR 0.837, 95% CI 0.745-0.939; p = 0.0024), cardiomyopathy (RR 0.651, 95% CI 0.543-0.780; p < 0.0001), neuropathy (RR 0.717, 95% CI 0.664-0.776; p < 0.0001), elevated liver enzymes (RR 0.608, 95% CI 0.516-0.716; p < 0.0001), and fever (RR 0.629, 95% CI 0.565-0.701; p < 0.0001). CONCLUSIONIn this large retrospective cohort, GLP-1 RA use was associated with significant reductions in hematologic, gastrointestinal, cardiovascular, and systemic toxicities among breast cancer patients receiving chemotherapy. These findings support the investigation of GLP-1 RAs as adjunctive agents in oncology supportive care. Prospective trials are needed to confirm these benefits and explore the underlying mechanisms, with the goal of integrating GLP-1 RAs into protocols to reduce treatment-related morbidity and improve patient outcomes.

C. Jones¹, J. Michalek², E. Obomanu³, Y. Arya⁴, A. Syal⁵, S. Haddad¹, V. Kaklamani¹, S. Shaikh¹; ¹Hematology/Oncology, University of Texas Health Science Center San Antonio, San Antonio, TX, ²Population Health Sciences, University of Texas Health Science Center San Antonio, San Antonio, TX, ³Internal Medicine, Jefferson Einstein Hospital, Philadelphia, PA, ⁴Hematology/Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, ⁵Hematology/Oncology, Mayo Clinic Jacksonville, San Antonio, FL.

Introduction Endocrine therapy (ET) improves survival in hormone receptor-positive breast cancer (BC) but has side effects that may affect compliance. GLP-1 receptor agonists (GLP-1 RA), used for diabetes and obesity, possess anti-inflammatory properties and may reduce cancer incidence. Their impact on all-cause mortality and ET tolerability remains underexplored. This real-world analysis is the first of its kind to examine the effects of GLP-1 RA on these outcomes. Methods We used de-identified data across 184 million patients and 156 health systems from the TriNetX database to identify obese women (BMI ≥30) with BC receiving ET (tamoxifen, anastrozole, exemestane, letrozole). Patients were grouped by GLP-1 RA exposure into age cohorts (≤50 and ≥51 years, as a surrogate for menopause). The primary endpoint was all-cause mortality; the secondary endpoint was ET tolerability. The index event was the first day meeting all criteria: BC and obesity diagnoses, and initiation of ET ± GLP-1 RA. Patients with outcomes before the study window were excluded. Propensity score matching performed by TriNetX adjusted for demographics, diabetes, comorbidities, cancer stage, and prior chemotherapy. Multivariate logistic regression assessed associations (risk ratios [RR], 95% CIs). Results After matching, 2,560 patients were assigned to the age ≤50 group: Cohort A (GLP-1 RA exposure, n=1,280) and Cohort B (non-exposure, n=1,280). Similarly, 26,468 patients were in the age ≥51 group: Cohort C (GLP-1 RA exposure, n=13,234) and Cohort D (non-exposure, n=13,234). In the ≤50 group, there was a mean age of 45.3 ± 4.4, 96.6% female, 59.5% White, 22.4% Black, and a mean BMI of 37 in Cohort A and similar in Cohort B. In the ≥51 group, there was a mean age of 68.3 ± 8.9, 96% female, 70.4% White, 16.3% Black, and a mean BMI of 37 in Cohort C and similar in Cohort D. GLP-1 RA use significantly reduced all-cause mortality in all cohorts. In the age ≤50 group, there were 14/1,270 events in Cohort A and 50/1,248 in Cohort B [RR 0.275 (0.153-0.495)]. In the age ≥51 group, there were 507/12,959 events in Cohort C and 1,153/12,702 in Cohort D [RR 0.431 (0.389-0.477)]. In the age ≤50 group, GLP-1RA reduced the incidence of hot flashes [RR: 0.515 (0.344-0.770)], pulmonary embolism (PE) [RR: 0.475 (0.225-1.005)], depression [RR: 0.634 (0.407-0.987)], nausea/vomiting [RR: 0.535 (0.363-0.788)], abdominal pain [RR: 0.471 (0.324-0.687)], diarrhea [RR:0.508 (0.319-0.807)] and dizziness [RR: 0.570 (0.375-0.867)]. No significant differences were found in DVT, endometrial cancer (EC), osteoporosis, joint pain, and fatigue. In the age ≥ 51 group, GLP-1 RA use reduced hot flashes [RR: 0.633 (0.541-0.741)], PE [RR:0.591 (0.482-0.724)], DVT [RR: 0.565 (0.460-0.645)], depression [RR: 0.661 (0.586-0.746)], osteoporosis [RR: 0.689 (0.620-0.765)], joint pain [RR: 0.767 (0.704-0.836)], fatigue [RR: 0.627 (0.565-0.697)], nausea/vomiting [RR: 0.735 (0.668-0.808)], abdominal pain [RR: 0.701 (0.639-0.768)], diarrhea [RR: 0.719 (0.649-0.796)], and dizziness [RR: 0.726 (0.659-0.800)]. No significant differences were noted in EC. Conclusion GLP-1 RAs were associated with reduced all-cause mortality and improved ET tolerability in obese BC patients. These findings support further investigation of metabolic interventions in BC care.

C. A. Ryals¹, A. Blarre¹, B. Adamson¹, D. Bower¹, G. G. Ho¹, O. Mbah¹, S. Radlein¹, E. Fidyk¹, F. Cody Stanford², A. B. Cohen¹; ¹N/A, Flatiron Health, New York, NY, ²Department of Medicine and Department of Pediatrics, Massachusetts General Hospital, Boston, MA.

Background: Obesity is a known risk factor for breast cancer (BC) incidence and recurrence. Glucagon-like peptide-1 (GLP-1) medications have emerged as effective treatments for weight management, with potential implications for oncology supportive care. However, their real-world use and impact among patients with BC remain poorly characterized. We extracted information from the electronic health record (EHR) using large language models (LLMs) to assess (1) documentation of GLP-1 use among patients with BC; (2) clinical, sociodemographic, and social determinants of health (SDOH) factors associated with GLP-1 use; and (3) the association between GLP-1 use and ctDNA testing and test results among a US-based cohort of patients with BC. Methods: We leveraged the US-based Flatiron Health Research Database, focusing on patients diagnosed with BC from January 2011 to February 2025. We used an LLM to extract GLP-1 medication details from unstructured EHR documents. We tested several prompt engineering strategies to optimize LLM extraction performance, including chain-of-thought and text curation techniques. We estimated a series of multivariable logistic regression models assessing associations between patient characteristics and GLP-1 use (i.e., documentation of GLP-1 use in EHR), sequentially adjusting for clinical factors (e.g., age, stage, year of diagnosis), sociodemographics (e.g., race/ethnicity), and SDOH (e.g., telemedicine use, practice setting, urban/rural). In exploratory analyses, we also estimated the unadjusted association between GLP-1 use and ctDNA testing (yes vs. no) and result (positive vs. negative) at any time. Results: Among our cohort of 967,968 patients diagnosed with BC, 64,400 (6.65%) patients had documented evidence of GLP-1 use and 16,689 (1.72%) patients underwent ctDNA testing. The LLM extracted GLP-1 use with high performance (F1 score = 0.94). Adjusted analyses revealed a higher likelihood of GLP-1 use among the following patient groups relative to their counterparts: patients with obesity (BMI≥30 vs. BMI75 vs aged 18-49; OR=0.54; 95%CI:0.46-0.64), advanced stage patients (stage IV vs. stage I OR=0.64; 95%CI:0.58-0.71), Latinx patients (vs. NL-White; OR=0.94; 95%CI:0.89-0.99), Asian patients (NL-White; OR=0.67; 95%CI:0.60-0.75), patients receiving care at community practices (vs. academic; OR=0.81; 95%CI:0.77-0.85), and those residing in neighborhoods with higher levels of limited English proficiency (high [LEP] vs. low LEP; OR=0.83; 95%CI:0.78-0.89) were less likely to have evidence of GLP-1 use. Compared with patients with no evidence of GLP-1 use, GLP-1 users had higher rates of ctDNA testing (OR=1.84; 95%CI:1.75-1.93) and a lower likelihood of ctDNA positivity (OR=0.76; 95%CI:0.67-0.85). Conclusions: Clinical, sociodemographic, and SDOH factors influence GLP-1 use among patients with BC. In exploratory analyses, we found that GLP-1 use was also associated with lower rates of ctDNA positivity, a biomarker linked to minimal residual disease and increased risk of recurrence. This study demonstrates the feasibility of using LLMs to extract GLP-1 medication details from the EHR, and helps lay the groundwork for future research evaluating the clinical impact of GLP-1 use on BC outcomes and recurrence risk, as well as equitable access to these therapies.

A. Y. Khan¹, F. A. Khan², M. Khan³, S. U. Safi¹, D. Safi¹; ¹Hematology/Oncology, West Virginia University, Morgantown, WV, ²Internal Medicine, Khyber Medical University, Peshawar, PAKISTAN, ³Endocrinology, West Virginia University, Morgantown, WV.

Background: Ductal carcinoma in situ (DCIS) is a non-invasive breast neoplasm that carries a risk of progression to invasive and metastatic disease. The potential impact of glucagon-like peptide-1 (GLP-1) receptor agonists, commonly used in diabetes management, on breast cancer outcomes in DCIS patients receiving hormonal therapy remains unclear.Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study comparing patients with DCIS on hormonal therapy with (Cohort 1, n=3,049) and without (Cohort 2, n=3,049) concomitant GLP-1 agonist use. Cohorts were propensity score matched on demographic, clinical, and laboratory parameters. The primary outcomes were the incidence of invasive and metastatic breast cancer, overall survival, and progression to stage IV disease over a 5-year period. Risk estimates, survival probability, hazard ratios (HR), and associated 95% confidence intervals (CIs) were calculated.Results: GLP-1 agonist use was associated with a significantly reduced risk of invasive and metastatic breast cancer (risk 4.1% vs 10.8%; risk difference -6.6%, 95% CI -7.9% to -5.3%; HR 0.36, 95% CI 0.29-0.44, p<0.001). Similarly, the risk of progression to stage IV disease was lower in the GLP-1 cohort (3.8% vs 10.6%; risk difference -6.7%, 95% CI -8.0% to -5.4%; HR 0.34, 95% CI 0.27-0.42, p<0.001). Overall survival was higher among GLP-1 users, with a 5-year survival probability of 93.5% compared to 85.7% in non-users (HR 0.37, 95% CI 0.29-0.47, p<0.001).Conclusions: In this large, real-world cohort, GLP-1 receptor agonist use was associated with significantly reduced risk of invasive/metastatic breast cancer and improved overall survival in patients with DCIS on hormonal therapy. These findings warrant further investigation through prospective trials to elucidate potential biological mechanisms and therapeutic implications.

D. Urueta Portillo, S. Haddad, E. Kaser, A. Baig, R. Banwait, M. Mazo Canola; Hematology Oncology, UT Health Mays Cancer Center, San Antonio, TX.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for weight and glycemic control and may have immunomodulatory effects relevant to cancer therapy. A recent study by Santos et al. (J Clin Oncol. 2025;43(16)_suppl:1115) found that GLP‑1 RA use was significantly associated with lower pathologic complete response (pCR) rates in Triple Negative Breast cancer patients (TNBC) undergoing neoadjuvant chemoimmunotherapy (30.8% vs 64.4%, p=0.001). Given the high prevalence of obesity and predominance of Hispanic patients at our center, we sought to evaluate this relationship in our population. Methods: We conducted a retrospective analysis of stage II-III TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (KEYNOTE‑522 regimen) between January 2018 and June 2025 at UT Health San Antonio Mays Cancer Center, which serves a predominantly Hispanic population with high rates of obesity. The KEYNOTE-522 regimen consisted of neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin or epirubicin and cyclophosphamide, with pembrolizumab continued postoperatively. Clinical data collected included age, BMI, race/ethnicity, GLP‑1 RA use, and pCR status (ypT0/Tis ypN0). Associations with pCR were assessed. Results: Seventy-seven patients were included; 16.7% (n=13) received GLP‑1 RAs. Median BMI was 29.5 for users vs 30.0 for non‑users. The cohort was 61.5% Hispanic, 16.7% non‑Hispanic White, 5.1% Asian, and 5.1% non‑Hispanic Black. pCR rates were similar between groups: 46.2% in GLP‑1 users vs 51.6% in non‑users (OR 0.81; p=0.77). BMI showed no association with pCR (p=0.95). Race/ethnicity was significantly associated with pCR (p<0.001), with Asian patients achieving a 100% pCR rate. Conclusions: In co ntrast to findings by Santos et al., GLP‑1 RA use was not associated with decreased pCR rates in our predominantly Hispanic, high‑BMI TNBC cohort. These results suggest that GLP‑1’s effect on treatment response may vary across patient populations. Given the limited sample size of this study, a larger multi-center analysis will be critical to more definitively assess the relationship between GLP‑1 use and pCR outcomes in diverse TNBC populations.

L. Chen¹, E. Canseco², K. Asadipour², Y. Yuan¹, S. L. Stephen²; ¹Hematology and Medical Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, ²Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA.

Title: GLP-1 Receptor Agonist in Combination with Radiotherapy Significantly Delays Tumor Growth and Improves Overall Survival in a Murine Model of Triple Negative Breast Cancer Authors: Luxi Chen, Elvin Canseco, Kamal Asadipour, Yuan Yuan, Stephen L. Shiao Institution: Cedars-Sinai Medical Center, Los Angeles, CA Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer that accounts for approximately 15-20% of all breast cancers and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. TNBC has the poorest prognosis among all breast cancer subtypes due to its molecular heterogeneity, high proliferation rate, and ability to undergo clonal evolution after treatment with chemotherapy. Despite remarkable improvement in the treatment of TNBC with chemoimmunotherapy (KEYNOTE-522, KEYNOTE-355), 37% of early-stage patients do not survive beyond the first 5 years following surgery. In the metastatic setting, the 5-year overall survival rate is a dismal 11%, highlighting the need for more effective therapies. A well-known significant risk factor for the development of TNBC is metabolic syndrome. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications approved for the treatment of type 2 diabetes mellitus and obesity that have garnered attention for their multifaceted roles beyond glycemic control, including in malignancy through modulating anti-tumor immunity and regulating signaling pathways involved in cancer cell growth and survival. Given their potential effect in breast cancer, we hypothesize that GLP-1RAs enhance the response to cytotoxic therapy, thereby delaying tumor growth and improving survival. Methods: Female C57BL/6 mice were inoculated with syngeneic EO771 TNBC cells, a murine model commonly used to mimic human TNBC, via intramammary injection in their lower mammary fat pads. Transplanted mice were treated when tumors achieved a minimum size of 300 mm³, at which time tumor-bearing mice were divided into the appropriate experimental cohorts with treatment groups receiving radiotherapy (RT) alone or radiotherapy combined with GLP-1 receptor agonist Exendin-4 (Ex-4). RT was given at a one-time dose of 16 Gy. Ex-4 was administered at a dosage of 30 nmol/kg body weight daily via IP injection. Tumor growth was quantitatively measured every 3 days throughout the studies using calipers until endpoint, defined as when the tumors reach a maximum size of 2000 mm³. Tumor size comparisons between experimental groups were analyzed using the 2-way ANOVA (Analysis of Variance) test. All end points were evaluated utilizing the Kaplan-Meier method. Hazard ratios (HR) were estimated using the Mantel-Haenszel method. All reported 95% confidence intervals (CI) are two-sided. Results: The results show that 14 days following RT, the combination of Ex-4 + RT (n = 6) significantly delayed tumor growth compared to RT alone (n = 7) (p = 0.0474). In addition, Ex-4 + RT significantly improved overall survival versus RT alone (HR 0.13, CI 0.03-0.59, p = 0.0081). The median survival of the RT cohort and Ex-4 + RT cohort were 18 days and 29 days, respectively, from the day of RT treatment. Additionally, we demonstrate that Ex-4-treated mice have altered immune cell composition compared to untreated mice, including changes in T cell subsets, B cells, and dendritic cells. Conclusion: Our results demonstrate that combination GLP-1RA and radiotherapy confers a significant delay in tumor growth and an improved overall survival benefit in a murine model of TNBC. Additional immunophenotypic and functional studies are ongoing to determine the mechanism by which combination treatment affects the anti-tumor immune response.