Abstract PD8-02: Evaluating weight loss outcomes in patients with hormone receptor-positive breast cancer on endocrine therapy receiving concurrent weight loss medications

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. Citation Format: T. Adamson, N. E. Gharaibeh, R. Shaw, C. D. Morrissey, S. Kapoor, A. Podolski, E. Teplinsky. Evaluating weight loss outcomes in patients with hormone receptor-positive breast cancer on endocrine therapy receiving concurrent weight loss medications [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 PD8-02.