Abstract PS3-05-08: Exploring Germline Genetic Testing Across a Diverse Ethnic Group with Triple-Negative Breast Cancer

Abstract Introduction: Triple-Negative Breast Cancer (TNBC) is the most aggressive form of breast cancer. Despite advancements in medical treatments, TNBC continues to be associated with a high likelihood of recurrence and poor outcomes. Gaining a deeper understanding of genetic profiles of TNBC is essential for identifying potential biomarkers, improving prognostic tools, and developing targeted therapies. This study aims to explore the baseline characteristics, survival outcomes, and genetic alterations in TNBC among a population with distinct ethnic backgrounds. Methods: Data on TNBC patients diagnosed and treated at the King Hussein Cancer Center who underwent germline genetic testing between 2014-2024 were retrospectively collected. Testing was performed on peripheral blood, and sequencing was done at international reference labs. Based on the date of testing, some patients underwent limited testing with only BRCA1/2 ± PALB2 (n=150), or an expanded multigene panel (n=432). Mutations were classified as benign/likely benign (negative), pathogenic/likely pathogenic (P/LP) (positive), or variant of uncertain significance (VUS). Event-Free Survival (EFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method to evaluate patient outcomes. Results: A total of 582 patients were included in the study, predominantly Jordanian (521, 89.5%), with a median age of 45 years (range: 37-54), and majority (548, 94.2%) presented with non-metastatic disease. Genetic testing revealed that 124 patients (21.3%) had P/LP variants, and 141 (24.2%) had VUS. The most frequent variants were BRCA1 (82, 66.1%) and BRCA2 (32, 22.8%). Other variants encountered (10, 8.1%) included PALB2, RAD51D, NF1, TP53, RAD51C, MLH1, BARD1, BRIP1, and MSH2. Rate of P/LP mutations were highest among younger patients aged 40 years (54/183, 29.5%) and lowest among patients 65 (3/36, 8.3%), p 0.001. Among the 124 patients with P/LP variants, 119 (96.0%) had a positive family history of cancer in a close relative. Of the 434 patients who underwent multigene panel testing, only 10 (2.3%) had mutations beyond BRCA1 and BRCA2, with just two in high-penetrance breast cancer-related genes (TP53 and PALB2). Risk-reducing contralateral mastectomy was performed by 79 (65.8%) patients with P/LP variants, while bilateral salpingo-oophorectomy was performed by 63 (52.5%). During follow-up, 28 patients (4.8%) experienced recurrence, and another breast cancer was diagnosed in 40 patients (6.8%), with a significantly higher rate observed among those with germline mutations (12.5% vs. 5.1%, p = 0.004). Conclusion: This study highlights the genetic characteristics of TNBC in an Arab population. The notably high prevalence of BRCA1 and BRCA2 pathogenic variants reinforces their central role in TNBC tumorigenesis. In resource-constrained settings, prioritizing genetic testing for these two genes offers a practical and cost-effective strategy. Although the prevalence of P/LP variants is significantly lower in patients over 65 years of age, it remains sufficiently substantial to justify continued testing in this group. Importantly, over half of mutation carriers opted for risk-reducing surgical interventions, reflecting the actionable value of genetic findings in clinical decision-making. Citation Format: H. Abdel-Razeq, T. Al-Batsh, F. Tamimi, B. Sharaf, H. Bani Hani, A. Al-Atary, L. El Saket, H. Khalil, Y. Talab, A. Issa, Z. Muhanna, O. Almuhaisen. Exploring Germline Genetic Testing Across a Diverse Ethnic Group with Triple-Negative Breast Cancer 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 PS3-05-08.