TMIC-07. pSTAT3 expression in patients with brain metastases from breast cancer: association with molecular subtypes and impact on overall survival

BACKGROUND A high pSTAT3 expression in reactive astrocytes (RA) of brain metastases (BrM) promotes tumor growth in preclinical models (Priego, 2018) and negatively affects the intracranial progression-free survival in BrM from breast cancer (BC) (Pellerino, 2023). We aim to evaluate whether pSTAT3 also impacts overall survival (OS). MATERIAL AND METHODS 105 BrM specimens from BC were identified from the University of Turin and RENACER network. pSTAT3 expression was scored in RA according to Priego, Nat Med 2018. Clinical and molecular data, and OS were retrospectively retrieved. RESULTS Median age was 55 years (95%CI 50,7-58,3). GFAP and pSTAT3 immunohistochemistry was feasible in 100/105 (95,2%). 21/100 patients (21%) had luminal BrM, 37/100 (37%) had HER2-positive BrM, and 42/100 (42%) triple-negative (TN) BrM. 88/100 (88%) specimens showed a positive pSTAT3 staining: 23/100 (23%) scored with 3, 34/100 (34%) with 2, 31/100 (31%) with 1, and 12/100 (12%) with 0 (negative). TNBrM showed higher pSTAT3 expression (34/42, 80.9%) in comparison to HER2-positive BrM (16/37, 43.2%) and luminal BrM (7/21, 33.3%) (p 0,002). Median OS of the whole cohort was 20 months (95%CI 15-28): high pSTAT3 BrM (score 2-3) had a shorter OS as compared with low pSTAT3 BrM (score 0-1) (32 months vs 13 months; HR 2,39; CI95% 1,49-3,87; p 0,0003). A shorter OS was observed in high pSTAT3 TNBrM as compared with low pSTAT3 BrM (10 months vs 28 months; HR 2,11; 95%CI 1,03 – 4,30; p 0,0041). TNBrM subtype (HR 1,63; 95%CI 1,11-2,39; p 0,0124), occurrence of intracranial recurrence after adjuvant treatments (HR 0,48; 95%CI 0,28-0,83; p 0,0081) and high pSTAT3 expression (HR 2,38; 95% CI 1,39-4,07; p 0,0016) retained statistical significance in multivariable analysis. CONCLUSION The positive correlation of high pSTAT3 expression with shorter survival in TNBrM suggests the chance to target STAT3 with specific inhibitor. A randomized trial in ongoing (NCTNCT05689619).