Risk of central nervous system metastasis and survival in HER2+ positive breast and non-breast cancers

Incidence, survival, and optimal choice of therapy for central nervous system (CNS) metastasis are well characterized in human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), yet remain poorly defined in other HER2+ solid tumors (STs).

A retrospective cohort analysis was performed to characterize the incidence of CNS metastasis and clinical outcomes in patients with HER2+ breast cancer and ST treated at the University of Virginia Emily Couric Cancer Center between January 2010 and January 2022.

In the cohort, 50 patients had HER2+ ST and 383 had HER2+ BC. Of the ST group, 48.0% received CNS imaging at diagnosis as compared to 2.9% of breast cancer patients (P < .001). Cumulative incidence of CNS metastasis at diagnosis was 4% in the ST vs 1% in the breast cancer cohort (P < .001). Cumulative incidence of CNS metastasis was 20% in ST vs 6.8% in breast cancer cohorts (P < .001). In ST patients with CNS metastasis, 50% received CNS surgery/radiotherapy plus HER2-targeted therapy and 30% received CNS surgery/radiotherapy alone. Overall survival (OS) was significantly poorer in ST (median 1.7 years) vs breast cancer (median 18.5 years) cohorts overall (P < .001), as well as among Stage IV patients (1 year for ST vs 6.3 years for breast cancer).

Patients with non-breast cancer HER2+ STs had higher risk of CNS metastasis and poorer OS compared to HER2+ breast cancer patients, with lower utilization of HER2-directed therapy.