Abstract PS4-07-11: Analysis of patients with triple-negative breast cancer and germline BRCA mutation undergoing neoadjuvant treatment following the keynote 522 protocol in real-world. Insights from the Neo-Real/GBECAM-0123 Study

Abstract Background The KEYNOTE-522 study established a new standard of care for early-stage triple-negative breast cancer (TNBC), demonstrating that the addition of pembrolizumab to neoadjuvant chemotherapy, followed by adjuvant pembrolizumab, significantly improves pathological complete response (PCR) rates, event-free survival (EFS), and overall survival (OS). BRCA1/2 mutations define a distinct molecular subgroup of TNBC, characterized by impaired DNA repair and potential differential sensitivity to platinum agents and immunotherapy. Real-world data on this subgroup remain limited. Methods Neo-Real/GBECAM-0123 is a multicenter, real-world study that included patients with early-stage TNBC treated with the KEYNOTE-522 regimen in Brazil and Argentina since July 2020. Patients were categorized as BRCA mutation carriers (mBRCA) or wild-type/unknown (wt/unkBRCA). Clinical, pathological, and treatment-related outcomes were compared using descriptive and inferential statistics. Results Among 726 patients, 104 (14.3%) were mBRCA and 622 (85.7%) were wt/unkBRCA (495 [84.2%] wild-type and 93 [15.8%] unknown). Patients with mBRCA were significantly younger at diagnosis (mean age: 40.2 vs. 45.3 years; p < 0.001). In both groups, the majority of patients had stage II (73.0% and 72.3%) and stage 3 (80.2% and 74.2%) tumors. The pCR rate was significantly higher in the mBRCA group (74.0% vs. 61.4%; p = 0.018). Mastectomy was performed more frequently in mBRCA patients (88.3% vs. 34.7%; p < 0.001), and radiation therapy was also administered less frequently (64.4% vs. 87.1%; p < 0.001). With a median follow-up of 22 months, 82 patients experienced disease recurrence or death. Two-year EFS rates were 92.3% in the mBRCA group and 86.0% in the wt/unkBRCA group (HR 0.51, 95% CI: 0.23-1.11; p = 0.091). Discussion This real-world analysis provides strong evidence that patients with triple-negative breast cancer (TNBC) with mBRCA experience distinct clinical characteristics and superior outcomes when treated with the KEYNOTE-522 regimen. The 12.3% absolute increase in the pCR rate translated into favorable EFS trends. These findings are clinically relevant and may guide future strategies for risk-adapted treatment de-escalation. Citation Format: M. C. Tavares, F. C. Balint, R. B. Barroso-Sousa, S. Sanches, L. Testa, G. Colucci, N. C. Nunes, B. G. Giner, M. Gill, I. S. Martins, M. Andrade, M. Gouveia, F. Madasi, J. Bines, R. Ferreira, D. Rosa, C. Santos, M. Monteiro, Z. S. Souza, D. Assad-Suzuki, C. Anjos, D. M. Gagliato, A. Gomes, B. Zucchetti, A. Ferrari, M. Brito, M. F. Monteiro, P. A. Signorini, N. J. Gomes, S. Mazzotta, P. M. Hoff, M. Estevez-Diz, R. R. Bonadio. Analysis of patients with triple-negative breast cancer and germline BRCA mutation undergoing neoadjuvant treatment following the keynote 522 protocol in real-world. Insights from the Neo-Real/GBECAM-0123 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 PS4-07-11.