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Molecular Diagnostics

Tumour-infiltrating CD4-, CD8- and FOXP3-positive immune cells as predictive markers of mortality in BRCA1- and BRCA2-associated breast cancer

British Journal of Cancer volume 125, pages 1388–1398 (2021)Cite this article

Subjects

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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Fig. 1: Representative examples of CD4, CD8 and FOXP3 staining patterns.
Fig. 2: Distribution of immune marker expression.
Fig. 3: Survival analysis.

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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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Authors and Affiliations

  1. Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology (CIRRI), Zealand University Hospital, Roskilde, Denmark

    Nanna Jørgensen & Thomas Vauvert F. Hviid

  2. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Nanna Jørgensen & Thomas Vauvert F. Hviid

  3. Danish Breast Cancer Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Lise B. Nielsen, Bent Ejlertsen & Maj-Britt Jensen

  4. Department of Surgical Pathology, Zealand University Hospital, Roskilde, Denmark

    Ida M. H. Sønderstrup, Jens Ole Eriksen & Anne-Vibeke Lænkholm

  5. Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Bent Ejlertsen

  6. Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Anne-Marie Gerdes

  7. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark

    Torben A. Kruse & Mads Thomassen

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Contributions

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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Correspondence to Thomas Vauvert F. Hviid.

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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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