Nanna Jørgensen1,2, Thomas Vauvert F Hviid3,4, Lise B Nielsen5, Ida M H Sønderstrup6, Jens Ole Eriksen6, Bent Ejlertsen5,7, Anne-Marie Gerdes8, Torben A Kruse9, Mads Thomassen9, Maj-Britt Jensen5, Anne-Vibeke Lænkholm6. 1. Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital, Roskilde, Denmark. 2. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 3. Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital, Roskilde, Denmark. tvh@regionsjaelland.dk. 4. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. tvh@regionsjaelland.dk. 5. Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark. 7. Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 8. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 9. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Abstract
BACKGROUND: The prognostic value of tumour-infiltrating lymphocytes (TILs) in breast cancer is well-established. However, the investigation of specific T-cell subsets exclusively in BRCA-associated breast cancer is sparse. METHODS: Tumour tissues from 414 BRCA-mutated breast cancer patients were analysed by immunohistochemistry and digital image analysis for expression of CD4, CD8 and FOXP3 immune markers. Distribution of CD4-, CD8- and FOXP3-positive cells and clinicopathological characteristics were assessed according to groups of low or high expression. The prognostic value was evaluated as continuous variables in univariate and multivariate analyses of overall survival and disease-free survival. RESULTS: Both CD4 and CD8 expression are associated with histological diagnosis, tumour grade and oestrogen and progesterone receptor expression status. CD4 expression is associated with BRCA gene status. A high percentage of tumour-infiltrating CD4-, CD8- or FOXP3-positive cells is significantly associated with lower mortality in BRCA1- and BRCA2-associated breast cancer and CD8-positive cells are associated with disease-free survival. No heterogeneity according to BRCA gene status was found for the prognostic value of the immune markers. CONCLUSIONS: The results support a prognostic role of specific T-cell subsets in BRCA-associated breast cancer and the promising potential of targeting the immune system in the treatment of these patients.
BACKGROUND: The prognostic value of tumour-infiltrating lymphocytes (TILs) in breast cancer is well-established. However, the investigation of specific T-cell subsets exclusively in BRCA-associated breast cancer is sparse. METHODS: Tumour tissues from 414 BRCA-mutated breast cancer patients were analysed by immunohistochemistry and digital image analysis for expression of CD4, CD8 and FOXP3 immune markers. Distribution of CD4-, CD8- and FOXP3-positive cells and clinicopathological characteristics were assessed according to groups of low or high expression. The prognostic value was evaluated as continuous variables in univariate and multivariate analyses of overall survival and disease-free survival. RESULTS: Both CD4 and CD8 expression are associated with histological diagnosis, tumour grade and oestrogen and progesterone receptor expression status. CD4 expression is associated with BRCA gene status. A high percentage of tumour-infiltrating CD4-, CD8- or FOXP3-positive cells is significantly associated with lower mortality in BRCA1- and BRCA2-associated breast cancer and CD8-positive cells are associated with disease-free survival. No heterogeneity according to BRCA gene status was found for the prognostic value of the immune markers. CONCLUSIONS: The results support a prognostic role of specific T-cell subsets in BRCA-associated breast cancer and the promising potential of targeting the immune system in the treatment of these patients.
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