Association of circulating tumor cells with CNS metastatic patterns and survival outcomes in HER2+ metastatic breast cancer.

e13027 Background: Central nervous system (CNS) metastases are a major complication of HER2+ metastatic breast cancer (MBC), contributing to poor prognosis. Circulating tumor cells (CTCs) offer a minimally invasive tool for disease monitoring, but their prognostic significance in patients with CNS metastases and association with survival outcomes have not been well established. This study examines CTC levels in patients with HER2+ MBC and CNS metastases and investigates their relationship with survival outcomes and patterns of CNS involvement. Methods: This retrospective study examined 108 patients with HER2+ MBC who had CTCs collected from blood samples between 2016–2024 under an IRB-approved protocol (NU16B06) at Northwestern University Robert H. Lurie Cancer Center. CTC enumeration was performed via CELLTRACKS (Menarini). Patients who developed CNS metastases, defined as parenchymal brain metastases (PBM) or leptomeningeal disease (LMD), with CTC samples collected within 6 months prior to radiographic CNS detection were included for analysis. Results: 35 patients with HER2+ MBC who developed CNS metastases were identified. The median age at diagnosis of CNS metastases was 55 (interquartile range [IQR]: 46–59). At the time of radiographic detection, 26 (74%) patients had PBM, 4 (11%) had LMD, and 5 (14%) had both. Prior to detection of CNS metastases, 29 (82.9%) patients had a total CTCs > 1 and 24 (68.6%) had total CTCs > 5. Median total CTCs was 9 (IQR: 1–99) and median HER2+ CTCs was 4 (IQR: 1–55). Total CTC levels did not significantly differ among patients presenting with PBM (median: 6, IQR: 1–49), LMD (median: 106, IQR: 79–164), or both (median: 19, IQR: 11–92) (p = 0.3). Similarly, HER2+ CTC levels were not significantly different among patients with PBM (median: 4, IQR: 1–22), LMD (median: 57, IQR: 41–63), or both (median: 0, IQR: 0–65) (p = 0.5). Higher total CTC levels within 6 months preceding CNS metastases were significantly associated with worse overall survival (OS) (hazard ratio [HR]: 1.008, 95% CI: 1.004–1.012, p < 0.001) and worse progression-free survival (PFS) (HR: 1.004, 95% CI: 1.000–1.007, p = 0.028). Higher HER2+ CTC levels in the 6 months preceding CNS metastases were also significantly associated with worse OS (HR: 1.013, 95% CI: 1.004–1.021, p = 0.003) and worse PFS (HR: 1.011, 95% CI: 1.002–1.020, p = 0.013). Conclusions: In this small cohort of patients with HER2+ MBC and CNS metastases, higher total and HER2+ CTC levels prior to CNS metastases were associated with worse OS and PFS. CTC levels did not significantly differ among patients with PBM, LMD, or both at the time of radiographic detection. These findings suggest that CTC enumeration may have prognostic value in patients with HER2+ MBC and CNS metastases. Further studies are needed to validate these associations and evaluate the potential clinical utility of CTCs in risk stratification for this patient population.