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Increased regulatory T-cell numbers distinguish high-risk breast cancer patients and those at risk of late relapse

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Background

We aimed to assess the clinical significance of tumour-infiltrating FOXP3+ regulatory T cells (TR) in breast cancer patients with long-term follow-up.

Methods

FOXP3+ TR were detected by immunohistochemistry with our new FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3+ lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS) (n = 62), from invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue from patients without cancer (n = 10) were determined. A median cutoff value of 15 defined patients with high numbers of TR.

Results

TR numbers were significantly higher in DCIS and invasive breast carcinomas when compared with normal breast, with invasive tumours having significantly higher numbers than DCIS (P = 0.001). High numbers of FOXP3+ TR identified patients with DCIS at increased risk of relapse (P = 0.04) and patients with invasive tumours having both shorter relapse-free (P = 0.004) and overall survival (P = 0.007). High TR numbers were present in high-grade tumours (P < 0.001), in patients with lymph node involvement (P = 0.01) and in estrogen receptor alpha (ER)-negative tumours (P = 0.001). Importantly, quantification of FOXP3+ TR identified a group at high risk of relapse, within the so-called good prognostic group of ER-positive patients (P = 0.005) and these patients have a prognosis as poor as those that lack ER expression. Multivariate analyses, in ER-positive patients, demonstrated that greater TR numbers independently conferred a significantly higher hazard ratio than that of tumour grade and nodal status for relapse-free and overall survival, respectively. Unlike conventional clinicopathological factors, high numbers of FOXP3+ TR identified patients at risk of late relapse after 5 years disease-free survival.

Conclusion

These findings indicate that quantification of FOXP3+ TR in breast tumours is valuable for assessing disease prognosis and progression, and represents a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after 5 years of tamoxifen treatment. Furthermore, tumour vaccination approaches in combination with targeting TR cells are just entering clinical trials and our data strongly suggest that such therapy would be beneficial for a significant proportion of breast cancer patients.

Acknowledgements

The authors would like to thank Breast Cancer Campaign for their research support.

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Bates, G., Fox, S., Han, C. et al. Increased regulatory T-cell numbers distinguish high-risk breast cancer patients and those at risk of late relapse. Breast Cancer Res 8, P31 (2006) doi:10.1186/bcr1586

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Keywords

  • Tamoxifen
  • Breast Cancer Patient
  • Estrogen Receptor Expression
  • Late Relapse
  • High Hazard Ratio