Abstract Background: Neoadjuvant chemoimmunotherapy (NACT-IO) has been the standard of care for high-risk early-stage triple-negative breast cancer (eTNBC) for over five years. However, data on predictive biomarkers and clinical factors associated with treatment response remain limited. This study evaluates the association of several factors with pathological complete response (pCR) following NACT-IO. BRCA1/2 mutations, present in ∼15-20% of TNBC cases, are linked to higher tumor mutational burden (TMB), potentially enhancing immunotherapy response. Angiotensin-converting enzyme (ACE) is intrinsically expressed in immune cells and may influence anti-tumor immunity. Additionally, immune-related adverse events (irAEs) occur in ∼30% of eTNBC patients receiving NACT-IO; while higher-grade irAEs have been linked to improved pCR, data on low-grade irAEs remain limited. Thus, we assessed how BRCA1/2 status, ACE inhibitor use, and irAE severity may impact response to NACT-IO. Methods: A retrospective analysis was conducted on eTNBC patients treated with NACT-IO at Henry Ford Hospital (Detroit, MI) between July 2021 and October 2024. Categorical variables were analyzed using Chi-square or Fisher exact tests; P 0.05 was considered significant. Results: Among 173 eligible patients, 14 (8%) had pathogenic BRCA1/2 mutations, 18 (10%) were on ACE inhibitors, 7 (4%) had grade 1 irAEs, and 51 (29%) had grade ≥2 irAEs. pCR rates were significantly higher among those with grade ≥2 irAEs versus those with grade 1 or no irAEs. No significant differences in pCR rates were seen by BRCA status or ACE inhibitor use, though BRCA-mutated patients showed a numerical trend toward higher pCR rates. Conclusion: pCR rates were significantly higher in patients with grade ≥2 irAEs. The low number of grade 1 irAEs may reflect underreporting. While BRCA1/2 mutation carriers had numerically higher pCR rates, this was not statistically significant, suggesting a potential improvement in response that warrants further study. Notably, ∼22% of patients lacked documented BRCA status, underscoring the need for universal genetic testing in TNBC. No significant association was found between ACE inhibitor use and surgical outcomes; however, larger studies are needed to clarify their potential impact on response to immunotherapy. Citation Format: A. Sweidan, J. Sherwood, M. Ahmed, S. Bai, H. Ali. Exploring Potential Predictive Factors for Immunotherapy Response in Early-Stage TNBC: Insights from a Retrospective Analysis 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 PS4-10-20.
Sweidan et al. (Tue,) studied this question.
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