PROGNOSTIC SIGNIFICANCE OF TUMOR-ASSOCIATED MACROPHAGES IN METASTATIC HER2-POSITIVE BREAST CANCER PATIENTS’ SURVIVAL

Recent studies indicate an essential role of the tumor microenvironment in the effectiveness of therapy and survival of patients with various types of cancers, including HER2-positive breast cancer. Tumor-associated macrophages are one of the most common immune cells of the tumor microenvironment, with both pro-tumorogenic and anti-tumorogenic properties.The aim of our study was to clarify the prognostic role of M1 (CD68+) and M2 (CD163+) macrophages in patients with metastatic HER2-positive breast cancer.Material and methods. We studied the tumor tissue of 78 patients with metastatic HER2-positive breast cancer. Tumor tissue samples underwent immunohistochemical examination with antibodies to CD68+ and CD163+ to determine the phenotype of M1 and M2 macrophages, respectively. Data on category T, category N and methods of drug therapy were obtained from primary medical records. Kaplan-Meier method, Cox regression analysis, and log-rank test were used for statistical analysis.Results. The average duration of the follow-up period before registration of disease progression was 21.3±2.79 months. Median progression-free survival was 14.3 months and 13.2 months for patients with high and low CD68+ expression, respectively (Log-rank p=0.6168), and 14.9 months and 12.6 months for patients with low and high expression of CD163+, respectively (Log-rank p=0.0003). Follow-up of patients until death continued for an average of 35.0±2.98 months. Median overall survival was 24.1 months and 29.0 months for patients with high and low CD68+ expression, respectively (Log-rank p=0.5788), and 36.7 months and 22.0 months for patients with low and high expression of CD163+, respectively (Log-rank p=0.0001). Patients receiving a combination of trastuzumab with chemotherapy, without regional lymph node metastases, with low expression of CD163+, and those with hormone-positive HER2-positive breast cancer used hormone therapy have better overall survival.Conclusions. High CD163+ expression is a predictor of poor progression-free survival and overall survival in patients with metastatic HER2-positive breast cancer. CD68+ expression did not show prognostic significance.