Heterogeneity of HER2 Expression in Circulating Tumor Cells of Patients with Breast Cancer Brain Metastases and Impact on Brain Disease Control

SIMPLE SUMMARY: Results from a previous study suggested that the number of circulating tumor cells (CTC) might have a role as a biomarker of early distant brain failure in patients with breast cancer brain metastases (BCBM). However, it remains largely underexplored whether heterogeneous HER2 expression in CTC may have a prognostic implication. We evaluated the status of HER2 expression in CTC before and after radiotherapy/radiosurgery for BCBM and observed that the presence of HER2 expression in any moment was associated with longer distant brain failure-free survival, irrespective of the primary immunophenotype of the breast tumor. This finding suggests that the status of HER2 expression in CTC has the potential to improve the treatment selection for patients with BCBM. ABSTRACT: HER2 expression switching in circulating tumor cells (CTC) in breast cancer is dynamic and may have prognostic and predictive clinical implications. In this study, we evaluated the association between the expression of HER2 in the CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. An exploratory analysis of a prospective assessment of CTC before (CTC1) and after (CTC2) stereotactic radiotherapy/radiosurgery (SRT) for BCBM in 39 women was performed. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. The median DBFFS was 10 months in patients without HER2 expressed in CTC and was not reached in patients with HER2 in CTC (p = 0.012). The median OS was 17 months in patients without HER2 in CTC and was not reached in patients with HER2 in CTC (p = 0.104). On the multivariate analysis, DBFFS was superior in patients who were primary immunophenotype (PIP) HER2-positive (HR 0.128, 95% CI 0.025–0.534; p = 0.013). The expression of HER2 in CTC was associated with a longer DBFFS, and the switching of HER2 expression between the PIP and CTC may have an impact on prognosis and treatment selection for BCBM.