Voxel-wise analysis of brain metastasis predilection sites in breast cancer by clinical features

Brain metastases (BMs) occur in 15-30% of breast cancer patients, particularly in HER2-positive and triple-negative(TN) subtypes, and signify poor prognosis. This study aimed to identify vulnerable BM locations through voxel-wise analysis of clinical characteristics.

We retrospectively analyzed 161 breast cancer patients with BMs (2007-2019) and performed voxel-wise MRI analysis using standardized templates. Segmentation results were superimposed on standard brain templates to construct stereo-specific frequency thermograms and compared under the same voxel. Two-tailed Fisher's exact test was performed. Overall survival (OS) and post-progression survival (PPS) after confirmation of brain metastases were tested by Kaplan-Meier, Cox regression analysis calculation, and log-rank test.

The frequency heat map shows lesions of patients with breast cancer brain metastases were more inclined to the cerebellar hemisphere. Older patients' lesions mainly occurred in the right frontal lobe, the left parietal lobe, and adjacent meninges compared with white matter of the right parietal lobe and cerebellar vermis among younger patients. ER-positive and PR-positive and HER2-overexpressed patients presented significance in the parieto-occipital lobe, cerebellum and adjacent meninges. Metastases with high levels of CEA were found in areas around the central anterior gyrus. HER2-overexpressed in primary sites and a normal level of serum CA15-3 were two independent protective factors in determining prognostic outcomes.

The preferred locations of breast cancer with brain metastases could be observed based on different clinical and biological characteristics, which could be clues for further study and helpful for clinical strategies.