Abstract PS5-05-28: Efficacy of systemic therapy in HER2-low breast cancer with CNS metastases: a “real-world” experience

Abstract Background: The incidence of central nervous system (CNS) metastases in breast cancer is increasing. While local treatments such as surgery and radiation remain standard, systemic therapies have shown promise in HER2-positive disease. However, data on the efficacy of systemic therapy in HER2-low breast cancer with CNS involvement remain limited. This study describes outcomes of upfront systemic therapy in HER2-low breast cancer patients with CNS metastases treated at a single institution. Methods: We retrospectively reviewed breast cancer patients with CNS metastases treated at Henry Ford Health between Jan 2014 and July 2024. HER2-low status was defined as: HER2 immunohistochemistry 1+, or 2+ with negative fluorescent in situ hybridization (FISH). Eligible patients received no concurrent local CNS therapy; prior local treatment was permitted if unrelated to the studied lesions. CNS responses were to be assessed using the Response Assessment in Neuro-Oncology for brain metastases (RANO-BM) or the modified RANO-LM (leptomeningeal metastases) criteria. Results: Sixteen HER2-low patients were included. The median age was 56 years (range, 38-93); 63% (n = 10) were African American. Most (75%) had hormone receptor-positive disease, and 53% presented with de novo metastatic disease. Thirteen patients (81%) had HER2 IHC 1+, and only three had HER2 IHC 2+/FISH-negative disease. The majority (88%) had parenchymal CNS metastases; one patient had leptomeningeal disease, and one had both. Eight patients (50%) had prior CNS metastases, and 38% received local therapy before study inclusion. Notably, a significant proportion of patients (88%) had non-measurable disease by RANO-BM criteria (lesions 10 mm threshold typically required for clinical trial eligibility, necessitating special attention and adapted approaches for response assessment. Citation Format: B. Ghimire, L. Rogers, M. Girgis. Efficacy of systemic therapy in HER2-low breast cancer with CNS metastases: a “real-world” experience [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 PS5-05-28.