MON-720 - Impact of Anti-Obesity Medications on Skeletal Muscle Mass and Body Composition in Patients with Hormone Receptor-Positive Breast Cancer Receiving Concurrent Endocrine Therapy

Estrogen is central to metabolic regulation & lean muscle preservation; its decline after menopause increases the risk of obesity, type 2 diabetes, & sarcopenia. Endocrine therapies (ET), including tamoxifen & aromatase inhibitors (AI), improve outcomes in hormone receptor-positive (HR+) breast cancer (BC) but may adversely affect metabolic health in a population where sarcopenia is common. Use of anti-obesity medications (meds), particularly GLP-1 receptor agonists (GLP-1 RAs), is increasing; however, in the general population, 25–30% of weight loss is attributable to lean muscle loss. Data in patients (pts) with BC receiving ET are limited. This retrospective study evaluated changes in body weight & muscle mass in pts with stage 0–IV HR+ BC treated with ET & anti-obesity meds.

We performed a retrospective review of 150 pts with HR+ BC seen at our institution’s metabolic clinic: 39 pts met eligibility criteria, including initiation of ET ≥3 months before anti-obesity meds, & ≥2 follow-up visits. Data collected included demographics, BC history, comorbidities, anti-obesity meds, body weight, & muscle mass measured by body composition analyzer. The primary endpoint was mean total body weight change at 3, 6, 9, & 12 months (mo), when available. Secondary endpoints included mean muscle mass changes at corresponding time points. Categorical variables were reported as percentages, & within-patient changes were analyzed using paired t-tests.

Median age was 53 years (range 38–69). N=27 pts had stage I BC; 36 pts were postmenopausal, & 5 pts had HR+/HER2+ BC. ET therapies at initiation of anti-obesity therapy: anastrozole (n=26), tamoxifen (n=7), exemestane (n=4), and letrozole (n=2), with a median ET duration of 38 months (range 5–108). Common comorbidities: hyperlipidemia (71.8%), prediabetes (38.5%), and type II diabetes (10.3%). 74% (n=29) received GLP-1 RA’s, while 28% (n=11) received oral anti-obesity agents; one pt received both. GLP-1 RA’s included tirzepatide (n=24), semaglutide (n=11), and liraglutide (n=3); oral agents were phentermine ± topiramate (n=11). Some pts switched therapies. Before treatment, mean total body weight was 195.2 lbs (n=39) and mean muscle mass was 57.6 lbs (n=37). At 6 months, 37 pts had mean weight loss of ~27 lbs (p < 0.001); among 26 pts with available data, muscle loss accounted for 12.8% of total weight lost. At 12 months, 19 pts lost ~41 lbs (p < 0.001), with lean muscle comprising 11.4% of total weight loss among 16 pts with available data.

In pts with HR+ BC on ET, GLP-1 RA’s & oral anti-obesity meds produced modest weight loss through 12 months, with significantly less muscle mass loss at 6 and 12 months compared with the general population. Limitations include use of body composition analyzer scales versus DEXA & grouping of agents together. Prospective studies are needed to assess long-term efficacy & better characterize sarcopenia in this population.

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