Clinical Risk Factors of CNS-Related Death in Patients With HER2+ MBC

To better understand the impact of central nervous system (CNS) relapse and brain metastasis on mortality, a single-institution medical chart review was conducted to determine the incidence of CNS-related death and to identify its risk factors associated in patients with HER2+ metastatic breast cancer (MBC).

Patients with HER2+ MBC and a diagnosis of CNS disease were treated at Memorial Sloan Kettering Cancer Center between August 2010 and April 2022. CNS-related death was defined as any death caused by brain metastasis or leptomeningeal disease (LMD) or dural metastases (DM) progression or CNS treatment–associated complications.

The analysis included a total of 274 evaluable patients. Overall, 63 of 275 (23%) patients presented with CNS as the first and only site of metastasis. Patients received a median of 1 line of systemic therapy pre- CNS disease diagnosis. Post-CNS metastasis, 43% of patients received a HER2 tyrosine kinase inhibitor, including tucatinib (18%).

In this cohort, the median follow-up was 3.7 years for survivors. Of the patients who died (192/274), more than half (55%) died of a CNS-related cause. The median overall survival (OS) was 2.10 years for the total cohort, but was longer in patients with brain metastasis only versus those with ECM ± brain metastases/dural metastases (3.57 years vs 2.01 years; P=.002). The cumulative incidence of CNS-related death at 3 years was 33%.

These results indicate that CNS involvement directly correlated with CNS-related death, with greatest risk in patients with LMD.


Ferraro E, Nassif RB, Reiner A, et al. Clinical risk factors of central nervous system (CNS)-related death in patients with HER2-positive metastatic breast cancer. Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PS11-02.

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