Background
Despite the known incidence of brain metastases in breast cancer, no useful biomarker has been clinically established for breast cancer brain metastasis (BCBM). In the present study, we aimed to examine the expression of microRNAs (miRNAs) related to BCBM in formalin-fixed paraffin-embedded (FFPE) tissues to identify their usefulness as predictive biomarkers of breast cancer brain recurrence (BCBR).

Methods
Pairs of primary breast and metastatic site tissue samples were collected from 38 patients who experienced the first recurrence of metastasis to a single distant organ (brain/lungs/liver/bones = 11/12/9/6 patients) between January 2007 and December 2021 at five institutions in Japan. We evaluated the expression of 15 miRNAs in FFPE specimens of untreated breast and metastatic sites from the same patient using quantitative polymerase chain reaction.

Results
Analysis of the selected 15 miRNAs revealed that hsa-miR-155-5p exhibited significant BCBR-specific overexpression in untreated primary breast tissues (p < 0.001). Two other miRNAs, hsa-miR-150-5p and hsa-miR-20b-5p, exhibited moderate (ρ = 0.587) and weak (ρ = 0.350) positive correlations with hsa-miR-155-5p, respectively. The BCBR prediction model demonstrated a high discrimination ability for hsa-miR-155-5p (AUC = 0.960). The localization of hsa-miR-155-5p in primary breast cancer tissue by in situ hybridization confirmed that hsa-miR-155-5p was uniformly stained in the breast cancer cells.

Conclusions
Hsa-miR-155-5p expression in untreated primary breast tissue may be a valuable biomarker for predicting BCBR. A personalized escalation strategy is expected to be helpful in conquering brain metastases.