Preclinical study

Breast Cancer Research and Treatment

, Volume 125, Issue 1, pp 65-72

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

  • Sylvain LadoireAffiliated withDepartment of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François LeclercInstitut National de la Santé et de la Recherche Médicale, University of DijonDepartment of Pathology and Molecular Biology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc
  • , Laurent ArnouldAffiliated withDepartment of Pathology and Molecular Biology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc
  • , Grégoire MignotAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of Dijon
  • , Bruno CoudertAffiliated withDepartment of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc
  • , Cédric RébéAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of DijonDepartment of Pathology and Molecular Biology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc
  • , Fanny ChalminAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of Dijon
  • , Julie VincentAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of Dijon
  • , Mélanie BruchardAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of Dijon
  • , Bruno ChauffertAffiliated withDepartment of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François LeclercInstitut National de la Santé et de la Recherche Médicale, University of Dijon
    • , François MartinAffiliated withInstitut National de la Santé et de la Recherche Médicale, University of Dijon
    • , Pierre FumoleauAffiliated withDepartment of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François Leclerc
    • , François GhiringhelliAffiliated withDepartment of Medical Oncology, Centre Regional de Lutte Contre le Cancer Georges François LeclercInstitut National de la Santé et de la Recherche Médicale, University of DijonDepartment of Pathology and Molecular Biology, Centre Regional de Lutte Contre le Cancer Georges François LeclercFaculté de Médecine, Centre Georges François Leclerc, Centre de Recherche INSERM 866 Email author 

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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.

Keywords

Foxp3 HER2 Breast cancer Tumor cells Neoadjuvant chemotherapy