Abstract Background: GLP-1 receptor agonists (GLP-1RAs) are commonly prescribed in the setting of obesity and diabetes. Weight gain is known to increase risk of breast cancer recurrence, and GLP-1RAs are being more commonly used to facilitate weight loss. GLP-1 is rapidly degraded by DPP4, leading to the development of DPP4 inhibitors. Mechanistically, GLP-1 receptor activation on tumor cells may activate several growth signaling pathways based on preclinical studies, and GLP-1RAs may have an inhibitory effect on inflammation. Both of these functions have the potential to alter rates of response to HER2 targeted neoadjuvant chemotherapy. The recent study by Santos et al. demonstrated lower rates of pCR among patients with triple-negative breast cancer that were on GLP-1RAs while on neoadjuvant chemotherapy regimens. Whether this holds true for patients with HER2-positive breast cancer is unknown. The purpose of this study is to determine the effect of GLP-1RA exposure on pCR rate in patients with HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). This population is notable for a high proportion of Hispanic patients and an increased rate of obesity compared to national averages, which may impact treatment response. Methods: We retrospectively analyzed HER2-positive breast cancer patients treated at UT Health Mays Cancer Center (MCC) from January 2021 to June 2025 with standard of care neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Patients were stratified by exposure to GLP-1 receptor agonists during neoadjuvant therapy. The primary endpoint was pathologic complete response (ypT0/is, ypN0). Age, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), diabetes status, hormone receptor (HR) status, race, and clinical stage were collected as covariates. Fisher’s exact, chi-square, and descriptive statistics summarized group differences. Results: Among 42 patients, 6 (14%) used GLP-1 receptor agonists. The pCR rate was 33% (2/6) in GLP-1RA users compared to 58% (21/36) in non-users (p=0.21). Among patients on other DM2 medications (n=9), the pCR rate was 56%, while it was 55% among those on no DM2 medications (n=33). GLP-1RA users had similar mean age (54.2 vs 54.1 years, p=0.98) and a higher mean BMI (33.8 vs 29.6 kg/m2, p=0.14) compared to non-users. GLP-1RA users were mostly HR-positive (83%), similar to non-users (71%). Pathologic complete response by HR status showed no significant difference: pCR was achieved in 69% (9/13) of HR-negative patients vs 48% (14/29) of HR-positive patients (p=0.32). The racial distribution was 40% Hispanic white (n=17), 36% non-Hispanic white (n=15), 14% non-Hispanic Black (n=6), 7% Asian (n=3), and 2% Hispanic Black (n=1), consistent with the diverse population served by our center. There was no significant association between race and pCR (p=0.44). Due to sample size, no multivariate analysis was performed. Conclusions: In this single-center cohort, GLP-1RA use during neoadjuvant TCHP was associated with a numerically lower pCR rate in HER2-positive breast cancer. Although not statistically significant, this trend supports the need for larger prospective studies to evaluate whether GLP-1RA exposure may reduce pCR rates. Citation Format: D. Urueta Portillo, M. Mazo Canola. Impact of GLP-1 Receptor Agonist Use on Pathologic Complete Response in HER2-Positive Breast Cancer Treated with Neoadjuvant TCHP 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 PS3-11-29.
Portillo et al. (2026) studied this question.