BSBM-12 STAT3 EXPRESSION IN BRAIN METASTASES FROM BREAST CANCER: CORRELATIONS WITH DIFFERENT MOLECULAR SUBTYPES AND CLINICAL OUTCOME

BACKGROUND: STAT3 expression in peritumoral reactive astrocytes (RA) of brain metastases (BM) from breast cancer (BC) may favor a pro-metastatic environment. MATERIAL AND METHODS: 105 BM specimens from BC were identified from the biobank of Pathology Unit of University of Turin and Spanish national BrM network (RENACER). pSTAT3 expression was scored in RA of peritumoral tissue according to Priego et al. (Nat Med 2018). Clinical, molecular data, and intracranial progression (i-PFS) were retrospectively retrieved. RESULTS: Median age was of 50 years (range 46–54). 31/105 patients (29.5%) had luminal BM, 35/105 (33.3%) had HER2-positive BM, and 39/105 (37.1%) had triple negative BM. Immunohistochemistry for GFAP and pSTAT3 was feasible in 88/105 (83.8%). 49/88 (55.7%) showed positive staining of pSTAT3, of which 15/88 (17%) scored with 3, 34/88 (38.6%) with 2, 28/88 (31.9%%) with 1, and 11/88 (12.6%) with 0 (negative). High pSTAT3 expression (score 2-3) was observed in 27/34 (79.4%) triple negative BM, and in 18/30 (60.0%) HER2-positive BM, while most of luminal BM (20/24 – 83.3%) had low or absent pSTAT3 expression. Median i-PFS was 16.0 months (range 7-80): low pSTAT3 BM (score 0-1) had a median i-PFS of 11 months versus 8 months for high pSTAT3 BM (score 2-3) (HR 0.4; p=0.0123). A shorter median i-PFS was observed in high pSTAT3 triple negative BM (4 months) as compared with low pSTAT3 BM (20 months). Conversely, i-PFS of high pSTAT3 BM (7 months) was similar to low pSTAT3 BM (7 months) in HER2-positive BC. CONCLUSION: pSTAT3 expression in RA of triple negative BM and HER-2 positive BM is higher than in luminal BM. Of note, patients with high pSTAT3 triple negative BM progressed earlier in comparison with those with low pSTAT3, suggesting that pSTAT3 expression has an influence on the outcome.