Tmic-01. stat3 expression in brain metastases from breast cancer: correlations with different molecular subtypes and clinical outcome

Abstract 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 Eighty-five 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 54 years (range 30–81). Immunohistochemistry for GFAP and pSTAT3 was feasible in 68/85 (80%). 15/68 patients (21.1%) had BM from luminal BC, 27/68 (39.7%) from HER2-positive BC, and 26/68 (39.2%) from TNBC. 56/68 (82.4%) showed positive staining of pSTAT3, of which 9/68 (13.3%) scored with 3, 26/68 (38.2%) with 2, 21/68 (30.9%%) with 1, and 12/68 (17.6%) with 0 (negative). High pSTAT3 expression (score 2-3) was observed in 17/27 (62.9%) BM from HER2-positive BC and in 15/26 (57.7%) BM from TNBC, while most of BM from luminal BC (12/15 – 80%) had low or absent pSTAT3 (score 0-1) (p=0.021). Overall i-PFS was 16 months (range 7-41): low pSTAT3 BM (score 0-1) had a median i-PFS of 21 months versus 12 months for high pSTAT3 BM (score 2-3). A shorter median i-PFS was observed in high pSTAT3 BM from TNBC (4 months) as compared with low pSTAT3 BM (11 months). Conversely, i-PFS of high pSTAT3 BM (7 months) was similar to low pSTAT3 BM (6 months) in HER2-positive BC. CONCLUSION pSTAT3 expression in RA of peritumoral tissue of BM from TNBC and HER2-positive BC is higher than in BM from luminal BC. Of note, patients with high pSTAT3 BM from TNBC progressed earlier in comparison with those with low pSTAT3, suggesting that pSTAT3 expression has an influence on the outcome.