Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse

Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (T-R) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive T-R were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue In = 10) were determined. A median cutoff of >= 15 defined patients with high numbers of T-R. Results T-R numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DICIS (P =.001). High numbers of FOXP3-positive T-R identified patients with DCIS at increased risk of relapse (P =.04) and patients with invasive tumors with both shorter relapse-free (P =.004) and overall survival (P =.007). High TR numbers were present in high-grade tumors (P <.001), in patients with lymph node involvement (P =.01), and in estrogen receptor (ER) -negative tumors (P =.001). Importantly, high numbers of T-R within ER-positive tumors identified high-risk patients (P =.005). Unlike conventional clinicopathologic factors, high numbers of FOXP3-positive T-R can identify patients at risk of relapse after 5 years. Conclusion These findings indicate that quantification of FOXP3-positive T-R in breast tumors is valuable for assessing disease prognosis and progression, and that T-R are an important therapeutic target for breast cancer. FOXP3-positive T-R represent a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after standard tamoxifen treatment.