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.
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Data availability
The datasets used and/or analysed in the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported financially by Region Zealand, Region of Southern Denmark, and ‘Den Forskningsfremmende Pulje i Region Sjælland’ at the Department of Clinical Medicine, University of Copenhagen.
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Study concepts and data acquisition: NJ, TVFH, IMHS, JOE, BE, AMG, TAK, MT and AVL. Study design: NJ, TVFH, JOE, BE, MBJ and AVL. Quality control of data and algorithms: NJ, JOE and AVL. Data analysis and interpretation: NJ, MBJ and AVL. Statistical analysis: LBN and MBJ. Manuscript preparation: NJ. All authors contributed to manuscript editing. All authors reviewed and approved the final version of the paper and provided their consent for publication.
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The Danish National Committee on Health Research Ethics (33483) and the Danish Data Protection Agency (2009-41-3611) approved the study. The study was performed in accordance with the Declaration of Helsinki.
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Jørgensen, N., Hviid, T.V.F., Nielsen, L.B. et al. Tumour-infiltrating CD4-, CD8- and FOXP3-positive immune cells as predictive markers of mortality in BRCA1- and BRCA2-associated breast cancer. Br J Cancer 125, 1388–1398 (2021). https://doi.org/10.1038/s41416-021-01514-7
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DOI: https://doi.org/10.1038/s41416-021-01514-7
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