Globally, breast cancer (BC) is the leading cause of female death and morbidity. Homologous recombination repair (HRR) is critical in BC. However, the prognostic role and immunotherapy response of HRR in BC remains to be clarified. Firstly, we identified HRR types in BC samples from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset (GSE42568) based on 65 HRR genes (HRRGs). A differentially expressed gene (DEG) list for different HRR types was generated. Then, the influences of gene sets composed of these DEGs on biological pathways and BC prognosis were explored. Next, we identified gene clusters based on gene sets composed of DEGs. Genes associated with prognosis for DEGs were identified using univariate Cox regression. Finally, the HRR score was constructed based on genes associated with prognosis. We analyzed how HRR score correlates with tumor mutation burden (TMB), immune cell infiltration (ICI), and immunotherapy response. Three HRR clusters were discovered. HRR subtype A demonstrated decreased infiltration and a high number of immunosuppressive cells with a poor prognosis. DEGs among various HRR types were predominantly enriched in cell cycle and genomic stability-related pathways. The prognostic model based on sixteen DEGs accurately predicted BC prognosis. The HRRGs were differentially expressed in three DEG clusters. TMB, ICI, and immunotherapy responses differed significantly between the high and low HRR groups (HSG, LSG). The HSG was distinguished by a high degree of ICI and low TMB. LSG had a better response to anti-PD-1 or anti-PD-1 and anti-CTLA4 combination therapy. This work revealed that HRR patterns would contribute to predicting prognosis and immunotherapy response in BC, which may benefit patients.

在全球范围内，乳腺癌（BC）是女性死亡和发病的主要原因。同源重组修复 (HRR) 在 BC 中至关重要。然而，HRR 在 BC 中的预后作用和免疫治疗反应仍有待阐明。首先，我们基于 65 个 HRR 基因 (HRRG)，从癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据集 (GSE42568) 中识别了 BC 样本中的 HRR 类型。生成了不同 HRR 类型的差异表达基因 (DEG) 列表。然后，探讨由这些DEG组成的基因组对生物学途径和BC预后的影响。接下来，我们根据由 DEG 组成的基因集识别了基因簇。使用单变量 Cox 回归鉴定了与 DEG 预后相关的基因。最后，根据与预后相关的基因构建HRR评分。我们分析了 HRR 评分与肿瘤突变负荷 (TMB)、免疫细胞浸润 (ICI) 和免疫治疗反应的相关性。发现了三个 HRR 簇。HRR A 亚型表现出浸润减少和免疫抑制细胞数量较多，预后不良。各种HRR类型中的DEG主要富集于细胞周期和基因组稳定性相关途径。基于 16 个 DEG 的预后模型准确预测了 BC 预后。HRRGs 在三个 DEG 簇中差异表达。高 HRR 组和低 HRR 组（HSG、LSG）之间的 TMB、ICI 和免疫治疗反应存在显着差异。HSG 的特点是 ICI 程度高和 TMB 低。LSG对抗PD-1或抗PD-1与抗CTLA4联合治疗有更好的反应。这项工作表明，HRR 模式将有助于预测 BC 的预后和免疫治疗反应，这可能使患者受益。