Abstract PS3-09-21: Evaluation of Sensitivity to Endocrine Therapy (SET) as a Prognostic Biomarker in the Latin American Breast Cancer Cohort Study

Abstract Background: The SET2,3 index, which combines the SETER/PR index—a measure of transcriptional activity related to estrogen and progesterone receptor (ER, PR) —with the baseline prognostic index (BPI), has been validated as prognostic and predict endocrine treatment sensitivity in hormone receptor-positive (HR+) breast cancers from U.S. and European patients. However, its prognostic utility remains to be determined in Latin American (LA) breast cancer patients, who possess a unique and diverse genetic admixture. Methods: Clinical and pathological retrospective data were collected from a multi-country Latin American cohort of breast cancer patients. Tumor subtypes were previously characterized using PAM50 classification, Ki67%, and immunohistochemical analysis for ER, PR, and Human Epidermal Growth Factor Receptor 2 (HER2) status. The SET2,3 index was measured using the QuantiGene Plex Assay on archival tumor tissue samples from the HR+/HER2 Negative (-) cancers, blinded to clinical outcomes. Disease-free survival (DFS) was compared across patient subgroups using the log-rank test, and hazard ratios (HRs) were estimated through Cox proportional hazards models. Results: A total of 292 patients were included, with 38 disease-free survival (DFS) events observed over a median follow-up of 7.15 years. In a multivariable Cox model, use of adjuvant endocrine therapy (Yes vs. No; HR 0.27; p 0.001) and SET2,3 index (Low vs High; HR 3.45; p 0.001) were independently prognostic for longer DFS. Among patients who underwent primary surgery, SET2,3 index was significantly associated with DFS (Low vs. High; HR 3.20; 95% CI: 1.48-6.91; p =0.002). SET2,3 index also predicted outcomes for those receiving adjuvant chemotherapy (Low vs. High; HR 3.66; 95% CI: 1.25-10.78; p =0.01) or endocrine therapy alone (Low vs. High; HR 3.13; 95% CI: 1.21-8.10; p = 0.01). When stratified by PAM50 subtype, SET2,3 was significantly prognostic in non-Luminal A tumors (n = 9084; Low vs. High; HR 5.19; 95% CI: 1.20-22.51; p =0.01) but not in Luminal A tumors (n =162;0 p =0.3). Similarly, SET2,3 was prognostic in patients with low Ki67 index (20%) (n=97 Low vs High; HR 4.79; 95% CI: 1.20-19.17; p =0.01), but not in those with a high Ki67 index (n=155 p=0.06). The SETER/PR index of endocrine transcriptional activity (continuous variable) was also prognostic in 198 patients who received adjuvant endocrine therapy (HR 0.31 per unit, 95%CI 0.17-0.59, p 0.001). It was not significantly prognostic in the subset of 46 patients who did not receive endocrine therapy (HR 0.59, 95%CI 0.26-1.38, p =0.23). Conclusions: Our preliminary results confirm the SET2,3 as a strong predictor of disease-free survival in breast cancer of Latin American patients, with high SET2,3 index indicating longer DFS. SETER/PR index of endocrine transcriptional activity was strongly prognostic for patients who received adjuvant endocrine therapy. Some limitations: Small sample size in some subsets, retrospective nature of the analysis and differences in use of endocrine therapy between countries.These findings highlight the importance of including diverse patients in clinical trials to better characterize population-specific factors influencing breast cancer outcomes. . Citation Format: M. Mazo Canola, A. Llera, K. Zhang, K. M. Tran, M. Jeon, D. Alves da Quinta, E. Abdelhay, N. Artagaveytia, A. Daneri-Navarro, B. Müller, O. Podhajcer, J. Retamales, W. Symmans, J. Gomez. Evaluation of Sensitivity to Endocrine Therapy (SET) as a Prognostic Biomarker in the Latin American Breast Cancer Cohort Study 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 PS3-09-21.