488 CNS-Only Disease is Associated With Longer Survival but High CNS-Related Mortality in Patients With HER2+ Breast Cancer

INTRODUCTION: Among patients with HER2+ metastatic breast cancer (MBC), one-half develop brain metastasis (BrM). Due to poorer drugs efficacy in the CNS than extracranially, patients with HER2+ MBC and CNS-only disease are a growing population. METHODS: Patients with HER2+ MBC with CNS disease including BrM, leptomeningeal (LMD) and/or dural metastasis treated in our Institution between 8/2010 and 4/2022 were included. Extracranial metastasis (ECM) was evaluated at the time of CNS-metastasis and at last follow-up/death. CNS-related death was defined as death from tumor-related brain injury, functional deficits/seizures, and/or complications of brain-directed therapies. OS was estimated using Kaplan-Meier methodology. RESULTS: 274 patients were included. At CNS metastasis diagnosis, 72/274 (26%) presented with CNS-only disease (63 without prior ECM diagnosis, and 9 with ECM in complete response), and 200/274 (73%) with concomitant ECM. Two patients had unknown ECM status. Among patients with CNS-only disease, 34/72 (47%) never developed ECM progression by the time of their last follow-up/death. Patients with CNS-only disease had longer OS than patients with CNS+ECM: 3.48 years (95% CI: 2.10–5.14) versus 1.96 years (95% CI: 1.62–2.27), respectively (p = 0.017).The cumulative incidence of CNS-related death at 3 years was 33% (27%–38 %), and did not differ between CNS+ECM versus CNS-only groups, p = 0.14, despite higher use of neurosurgical resection in the latter group. Conversely, death due to other causes was more likely to occur in the CNS+ECM group than CNS-only, p = < 0.001. LMD and WBRT were independently associated with CNS-related death (HR = 1.88 [95% CI: 1.20–2.95], p = 0.006; HR = 1.69 [95% CI: 1.12–2.54], p = 0.01). CONCLUSIONS: With higher rates of local therapy, patients with CNS-only disease had longer survival but high rates of CNS-related death owing to the treatable but ultimately refractory disease nature. Novel therapies with CNS efficacy are urgently needed.