Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse.
OBJECTIVE
To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (TR) in breast cancer patients with long-term follow-up.


METHODS
FOXP3-positive TR 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 (n = 10) were determined. A median cutoff of > or = 15 defined patients with high numbers of TR.


RESULTS
TR numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive TR 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 < or = .001), in patients with lymph node involvement (P = .01), and in estrogen receptor (ER) -negative tumors (P = .001). Importantly, high numbers of TR within ER-positive tumors identified high-risk patients (P = .005). Unlike conventional clinicopathologic factors, high numbers of FOXP3-positive TR can identify patients at risk of relapse after 5 years.


CONCLUSIONS
These findings indicate that quantification of FOXP3-positive TR in breast tumors is valuable for assessing disease prognosis and progression, and that TR are an important therapeutic target for breast cancer. FOXP3-positive TR represent a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after standard tamoxifen treatment.
Bates
Gaynor J
GJ
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital; Cancer Research UK Molecular Oncology Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. gaynor.bates@ndcls.ox.ac.uk
Fox
Stephen B
SB
Han
Cheng
C
Leek
Russell D
RD
Garcia
José F
JF
Harris
Adrian L
AL
Banham
Alison H
AH
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology*; D018791:CD4 Lymphocyte Count; D002278:Carcinoma in Situ / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000473:pathology* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000473:pathology* / Q000556:secondary; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000473:pathology*
D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors