Presence of Foxp3 Expression in Tumor Cells Predicts Better Survival in HER2-Overexpressing Breast Cancer Patients treated wit

Purpose: The Forkhead Box Protein 3 is highly expressed in regulatory T cells, but also in tumor cells, acting as a transcriptional repressor of breast oncogenes including HER2. We investigated the prognostic significance of Foxp3 expression in cancer cells in a large cohort of patients with HER2-overexpressing breast carcinoma treated with neoadjuvant chemotherapy. Methods: Foxp3-positive tumor cells were detected by immunohistochemistry in 103 patients with primary invasive HER2-overexpressing breast carcinoma, and treated with neoadjuvant chemotherapy, with or without trastuzumab. Kaplan-Meier analysis and Cox regression model were used to assess relapse-free and overall survival, according to the presence or absence of Foxp3 expression in tumor cells. Results: Breast cancer cells were Foxp3+ in 57% of tumors. Foxp3 expression in breast cancer cells was associated with better relapse-free (P = 0.005), and overall survival (P= 0.03). By multivariate analysis, presence of Foxp3+ tumor cells resulted an independent prognostic factor both for better relapse-free (P = 0.006), and overall survival (P= 0.03). Conclusions: These findings indicate that the presence of Foxp3+ tumor cells represents a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma, which could help to select high risk patients for additional therapies after neoadjuvant chemotherapy.