Effect of HER2-low status on brain metastasis-free survival and survival after brain metastasis in patients with breast cancer.

Aims And Objectives: The discovery of novel human epidermal growth factor receptor 2 (HER2)-directed antibody‒drug conjugates has accelerated the identification of the HER2-low subtype. However, the biological significance of low HER2 expression in breast cancer brain metastasis (BCBM) is unclear.

Methods: Patients with HER2-negative BC and brain metastasis were retrospectively screened between February 2012 and November 2023. Brain metastasis-free survival (BMFS) and survival after brain metastasis (SABM) were analyzed according to HER2 expression.

Results: A total of 201 female patients, 84 of whom were HER2-low and 117 of whom were HER2-zero, were evaluated. The median BMFS in the entire cohort was 35.6 months (95% CI 29.8-41.4). Although HER2-low patients had numerically longer median BMFS than HER2-zero patients (43.7 m vs. 30.1 m, p = 0.025), multivariate analysis revealed that the difference was not significant (p = 0.167). BMFS between the HER2-low and HER2-zero groups was similar in the hormone receptor (HR)-positive (52.8 m vs. 47.6 m, p = 0.276) and HR-negative (15.3 m vs. 19.7 m, p = 0.930) cohorts. The median SABM in the entire cohort was 6.0 months (95% CI 3.8-8.1). HER2-low and HER2-zero patients had similar median SAMB (5.4 m vs. 6.1 m, p = 0.816). The SABM between the HER2-low and HER2-zero groups was similar in the HR-positive (6.3 m vs. 8.7 m, p = 0.375) and HR-negative (3.3 m vs. 4.2 m, p = 0.783) cohorts.

Conclusions: Low HER2 expression does not affect BMFS or SAMB in brain metastatic breast cancer patients in this real-world population.