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Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy

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Abstract

The Forkhead Box Protein 3 is highly expressed not only 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. 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, respectively, and according to the presence or the absence of Foxp3 expression in tumor cells. 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, the presence of Foxp3+ tumor cells produced an independent prognostic factor for both better relapse-free (P = 0.006) and overall survival (P = 0.03). 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 identify high-risk patients for additional therapies after neoadjuvant chemotherapy.

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Acknowledgments

This study was supported by Ligue contre le Cancer comité de Côte d’Or, Association pour la Recherche Contre le Cancer (ARC), Fondation de France INSERM AVENIR program and GERTI (Groupe d’Etude et de Recherche en Thérapeutique Innovante). Gregoire Mignot was supported by ARC (Association pour la Recherche contre le Cancer), and Julie Vincent by INCa (Institut National du Cancer).

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Authors and Affiliations

  1. Department of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc, Dijon, France

    Sylvain Ladoire, Bruno Coudert, Bruno Chauffert, Pierre Fumoleau & François Ghiringhelli

  2. Institut National de la Santé et de la Recherche Médicale, University of Dijon, Avenir Team INSERM. CRI-866, Dijon, France

    Sylvain Ladoire, Grégoire Mignot, Cédric Rébé, Fanny Chalmin, Julie Vincent, Mélanie Bruchard, Bruno Chauffert, François Martin & François Ghiringhelli

  3. Department of Pathology and Molecular Biology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc, Dijon, France

    Sylvain Ladoire, Laurent Arnould, Cédric Rébé & François Ghiringhelli

  4. Faculté de Médecine, Centre Georges François Leclerc, Centre de Recherche INSERM 866, 7 Boulevard Jeanne d’Arc, 21000, Dijon, France

    François Ghiringhelli

Authors
  1. Sylvain Ladoire
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  2. Laurent Arnould
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  3. Grégoire Mignot
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  4. Bruno Coudert
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  5. Cédric Rébé
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  6. Fanny Chalmin
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  7. Julie Vincent
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  8. Mélanie Bruchard
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  9. Bruno Chauffert
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  10. François Martin
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  11. Pierre Fumoleau
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  12. François Ghiringhelli
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Correspondence to François Ghiringhelli.

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Ladoire, S., Arnould, L., Mignot, G. et al. Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 125, 65–72 (2011). https://doi.org/10.1007/s10549-010-0831-1

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  • DOI: https://doi.org/10.1007/s10549-010-0831-1

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