Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab

Disease outcomes of HER2+ breast cancers have dramatically changed after targeted therapies, such as trastuzumab, came to clinical practice but predictive factors for trastuzumab sensitivity and resistance are frequently unknown. Current work included metastatic breast cancer patients (n = 48), who were treated with trastuzumab and had pre-treatment tumour samples available. The tumours were immunostained for T-cell (CD3, CD8), natural killer (NK)-cell (CD56) and macrophage (CD68) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumour locations. High number of CD3 and CD8 positive T-cells was associated with significant survival benefit in the center of the tumour (CT) (p = 0.007, p = 0.001) but not in the invasive margin. The number of NK-cells and macrophages in the CT showed non-significant tendency towards improved survival. In subgroup analyses, high density of CD8 CT cells was associated with significant survival benefit in non-bone only disease, in TX or T1-3, and in ER+ tumours (p = 0.006, p = 0.003, p = 0.001). Moreover, high CD8 CT cell density associated significantly with long trastuzumab interruption periods in response. The results suggest important prognostic and predictive role of tumour infiltrating lymphocytes in center of the tumours in metastatic HER2+ breast cancer.