Abstract PS2-02-26: Treatment patterns and prognosis of patients with HER2-negative early breast cancer and germline pathogenic variants in BRCA1, BRCA2, ATM, CHEK2 and PALB2

Abstract Introduction: There is conflicting evidence on the prognosis of patients with HER2-negative early breast cancer (HER2- eBC) and germline pathogenic variants (PV) including BRCA1, BRCA2, PALB2, ATM, and CHEK2. Studies are limited by marked heterogeneity and a small number of evaluable patients. Here, we present treatment patterns and prognosis in hereditary breast cancer(BC) susceptibility gene mutation carriers with HER2- eBC from CancerLinQ, a health technology platform comprised of de-identified real-world data from over 2.5 million patients across the United States. Methods: Patients with stage I-III HER2- eBC diagnosed between 2002-2023 were identified in CancerLinQ. Those with germline PVs in BRCA1, BRCA2, PALB2, ATM, and CHEK2 constituted the mutation carrier (MC) group while those with negative genetic testing made up the non-MC group. Demographics, pathology findings, genomic testing, and cancer treatment data were extracted. Patients with metastases within 9 months of diagnosis, and patients without stage information, and those without germline genetic testing were excluded. The primary outcome was recurrence free survival (RFS). Secondary objectives included overall survival (OS) and utilization rate of contralateral prophylactic mastectomy (CPM) in each group. RFS and OS were presented with Kaplan-Meier curves and were analyzed with the Cox proportional hazard regression method. Results: 1105 patients with germline PVs in BRCA1 (360,32.6%), BRCA2 (461,41.7%), PALB2 (76,6.9%), ATM (67,6.1%), and CHEK2 (91,8.2%) constituted the MC cohort; the non-MC cohort included 2129 patients. The MC cohort had a younger age at diagnosis and a higher rate of triple negative and nodal disease (p0.05). The MC group also received neoadjuvant chemotherapy more frequently and had a higher pathologic complete response rate. The adjusted RFS was improved for the non-MC group (HR 0.84,p=0.019) in comparison to the MC cohort; however, there was no statistically significant difference in OS between groups or by gene mutation. CPM use was more common in patients younger than 50 years and differed by gene mutation (p0.05). CPM vs breast conserving therapy or therapeutic mastectomy showed improved adjusted RFS (p=0.04) and OS (p=0.007) in the MC cohort. Black patients demonstrated worse OS (HR 1.3,p=0.005) regardless of MC status. Conclusions: This is one of the largest real-world analyses of hereditary BC susceptibility gene MCs with HER2- eBC. The MC group reported worse RFS. CPM use was more common in younger patients and in those with PVs in BRCA1/2. CPM use was independently associated with improved OS in MC group. This highlights the need for timely genetic testing and identification of at-risk patients who will benefit from personalized treatment approaches. Citation Format: V. Prasath, A. N. Riner, J. Kim, A. Clark, B. Slover, R. Wesolowski, J. C. Kai, S. Jhawar, C. Spears, B. A. Oppong, S. D. Sardesai. Treatment patterns and prognosis of patients with HER2-negative early breast cancer and germline pathogenic variants in BRCA1, BRCA2, ATM, CHEK2 and PALB2 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 PS2-02-26.