Abstract PD8-09: Revisiting the GLP-1-pCR Link in TNBC: Contrasting Outcomes in a High-BMI, Majority-Hispanic Cohort

Abstract 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. Citation Format: D. Urueta PortilloS. HaddadE. KaserA. BaigR. BanwaitM. Mazo Canola. Revisiting the GLP-1-pCR Link in TNBC: Contrasting Outcomes in a High-BMI, Majority-Hispanic Cohort [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 PD8-09.