P11.26.A STAT3 expression in brain metastases from breast cancer: correlations with different molecular subtypes and clinical outcome

Abstract

Abstract Background STAT3 expression in peritumoral reactive astrocytes (RA) of brain metastases (BM) may favor a pro-metastatic environment. The aim of the study was to evaluate in a retrospective cohort of surgically resected BM from breast cancer (BC) the expression of pSTAT3 in RA of peritumoral tissue of BM, identify different patterns of expression according to molecular subtypes, and correlate with intracranial progression-free survival (i-PFS). Material and Methods Patients with histologically proven BM diagnosis from BC were identified from the biobank of Pathology Unit of University of Turin and Spanish national BrM network (RENACER). pSTAT3 expression was evaluated and scored in RA of peritumoral tissue using GFAP and STAT3 immunohistochemistry, according to Priego et al. (Nat Med 2018). Data on histological diagnosis, molecular subtypes, and i-PFS were retrieved by chart review. Intracranial progression was defined based on MRI reports. Results Eighty-five BM specimens from BC of 85 female patients with a median age of 54 years (range 30-81 years) were available for analysis. Immunohistochemistry for GFAP and pSTAT3 was feasible in 68/85 (80%). Fifteen out of 68 patients (21.1%) had BM from luminal BC, 27/68 (39.7%) from HER2-positive BC, and 26/68 (39.2%) from TNBC. Fifty-six out of 68 (82.4%) showed positive staining of pSTAT3 in peritumoral RA, of which 9/68 (13.3%) scored with 3, 26/68 (38.2%) with 2, and 21/68 (30.9%%) with 1, while pSTAT3 expression was negative (score 0) in 12/68 (17.6%). 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.