The prognostic significance of FOXP3 expression in patients with metastatic HER2-positive breast cancer

Background. The effectiveness of targeted therapy in patients with HER2+ breast cancer largely depends on the tumor microenvironment. Regulatory T-lymphocytes (FOXP3+) negatively regulate immune responses and are mostly considered a factor of unfavorable prognosis. Breast cancer is a heterogeneous disease with unique biological properties for each molecular subtype. The impact of regulatory T cells on the prognosis of HER2+ breast cancer is controversial. Purpose – to evaluate the prognostic significance of regulatory T cells in patients with metastatic HER2+ breast cancer. Materials and Methods. The study included 78 patients with HER2+ breast cancer who were treated at the Sumy Regional Clinical Oncology Center from 2014 to 2024. Data on clinical and pathological characteristics of patients were taken from the primary medical documentation. Immunohistochemistry was performed for all samples of tumor tissue. Regulatory T lymphocytes were visualized using antibodies against FOXP3. Pearson test, One-way ANOVA, Kaplan–Meier method, and logarithmic test were used for statistical analysis. The Local Ethics Committee of the Sumy Regional Clinical Oncology Center approved the study. Results. The mean age of patients with low and high Foxp3 expression was 53.1 ± 1.74 and 57.3 ± 1.64, respectively. Among patients with high Foxp3 expression, there was a high proportion of women younger than 50 years (p = 0.0423) and estrogen-negative breast cancer (χ2 = 8.4080, p = 0.023). Other clinicopathological characteristics of the patients, such as the location of the primary tumor, histopathological diagnosis, the tumor grades, visceral and non-visceral metastases, and the Ki67 proliferation index, did not show an association with Foxp3 expression. Median progression-free survival was 12.9 months and 15.5 months for patients with low and high Foxp3 expression, respectively (Log-rank p = 0,0001). Median overall survival was 21.6 months and 46.9 months for patients with low and high Foxp3 expression, respectively (Log-rank p = 0,0001). Conclusions. In patients with metastatic HER2+ breast cancer, high Foxp3 expression is associated with better progression-free and overall survival. Among those with high FOXP3 expression, women under 50 years and with estrogen-negative breast cancer are more prevalent.