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.

中文翻译：

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肿瘤浸润性 CD4、CD8 和 FOXP3 阳性免疫细胞作为 BRCA1 和 BRCA2 相关乳腺癌死亡率的预测标志物

背景

肿瘤浸润淋巴细胞 (TIL) 在乳腺癌中的预后价值已得到公认。然而，专门针对BRCA相关乳腺癌的特定 T 细胞亚群的研究很少。

方法

来自 414名BRCA突变乳腺癌患者的肿瘤组织通过免疫组织化学和数字图像分析来分析 CD4、CD8 和 FOXP3 免疫标记物的表达。根据低表达或高表达组评估 CD4、CD8 和 FOXP3 阳性细胞的分布和临床病理学特征。在总生存期和无病生存期的单变量和多变量分析中，将预后值作为连续变量进行评估。

结果

CD4 和 CD8 表达均与组织学诊断、肿瘤分级以及雌激素和孕激素受体表达状态相关。CD4 表达与BRCA基因状态相关。高比例的肿瘤浸润性 CD4、CD8 或 FOXP3 阳性细胞与BRCA1和BRCA2相关乳腺癌的较低死亡率显着相关，而 CD8 阳性细胞与无病生存相关。对于免疫标志物的预后价值，未发现根据BRCA基因状态的异质性。

结论

结果支持特定 T 细胞亚群在BRCA相关乳腺癌中的预后作用，以及靶向免疫系统治疗这些患者的潜力。