206P Prognostic role of tumor-infiltrating lymphocytes (TILs) in first-line HER2-positive (HER2+) metastatic breast cancer (BC): A real-world study

In HER2+ early BC, several studies examined TILs as prognostic indicators and predictors of response, consistently revealing a positive correlation. Data on the role of TILs in advanced disease are limited. We conducted a retrospective study on patients (pts) with stage IV HER2+ BC treated at the European Institute of Oncology between June 2013 and January 2024, using pertuzumab, trastuzumab, and taxane-based chemotherapy as first-line therapy. We collected 1 archival sample for each patient (46 from the metastatic site and 34 from the primary tumor), obtained before the start of treatment. TILs were evaluated on Haematoxylin and Eosin (H&E)-stained slides, according to the International TILs Working Group criteria. TILs were analyzed both as continuous variables and dichotomized into low vs high, with the median TILs value in the study population as cutoff. Correlative analyses were conducted, with significance set at p-value<0.05. 80 consecutive pts were enrolled in the study, of whom 42 and 38 had hormone receptor-positive (HR+) and HR-negative (HR-) BC respectively. At the time of diagnosis, 57 pts (71.25%) had visceral disease, 30 pts (37.5%) had de novo metastatic disease, and 6 (7.5%) pts exhibited brain metastases (BMs). The median expression of TILs resulted to be 10% with 72.5% (58 pts) showing TILs expression of ≥10% (high-TILs). No statistically significant correlation was observed between TILs and ER expression, whether evaluated continuously or dichotomously (cut-off of 10%). Similarly, no correlation was found between TILs and HER2 expression, which was assessed dichotomously as 2+ ISH+ vs 3+. Furthermore, there was no correlation between the percentage of TILs and clinical outcomes, including progression-free survival (PFS) and overall survival (OS), even at multivariate analysis. Interestingly, TILs expression of ≥10% was associated with the presence of BMs at the time of diagnosis (p=0.035). Based on our analysis, it seems that TILs expression does not play a prognostic role in first-line treated HER2+ BC. However, confirming the correlation with BMs at diagnosis would necessitate a larger case study.