为确定人表皮生长因子受体2阳性（HER2 +）乳腺癌在使用曲妥珠单抗治疗后复发所涉及的遗传和免疫特征，我们进行了一项回顾性队列研究，对接受曲妥珠单抗治疗的48名患者进行了分组，根据临床随访结果将其分为复发和非复发组。对所有48名患者的基线样本进行了遗传变异、HLA等位基因型、基因表达和免疫特征的分析，这些特征与HER2 +乳腺癌的复发有关。统计学分析包括Logistic回归模型、Kaplan-Meier图和单变量Cox比例危害模型。与非复发组相比，复发组的细胞外基质相关通路和3个Hallmark基因集富集。不成熟B细胞和活化B细胞的浸润水平在非复发组中明显增加，与两个已发表的基因表达数据集（包括TCGA和METABRIC）中的整体生存（OS）显著相关。在TCGA队列（n = 275）中，激活的B细胞（HR 0.23，95％CI 0.13-0.43，p <0.0001）和不成熟的B细胞（HR 0.26，95％CI 0.12- 0.59，p <0.0001）。在METABRIC队列（n = 236）中，激活的B细胞（HR 0.60，95％CI 0.43-0.83，p = 0.002）和不成熟的B细胞（HR 0.65，95％CI 0.47-0.91，p = 0.011）。 Cox回归分析表明，不成熟的B细胞和激活的B细胞是预后OS的保护因素，多条通路异常激活和基线肿瘤浸润B细胞低是与HER2 +乳腺癌曲妥珠单抗治疗复发相关的主要因素，这主要影响曲妥珠单抗的抗肿瘤活性。 © 2023年。作者（s）独家许可Springer Science + Business Media，LLC，Springer Nature的一部分。

To determine the genetic and immune features associated with the recurrence of human epidermal growth factor receptor2-positive (HER2 +) breast cancer (BC) after trastuzumab-based treatment.A retrospective cohort study of 48 patients who received trastuzumab-based treatment was divided into recurrent and non-recurrent groups according to clinical follow-up. Baseline samples from all 48 patients were analyzed for genetic variation, HLA allele type, gene expression, and immune features, which were linked to HER2 + BC recurrence. Statistics included logistic regression models, Kaplan-Meier plots, and Univariate Cox proportional hazards models.Compared with the non-recurrent group, the extracellular matrix-related pathway and 3 Hallmark gene sets were enriched in the recurrent group. The infiltration levels of immature B cells and activated B cells were significantly increased in the non-recurrent group, which correlated remarkably with improved overall survival (OS) in two other published gene expression datasets, including TCGA and METABRIC. In the TCGA cohort (n = 275), activated B cells (HR 0.23, 95%CI 0.13-0.43, p < 0.0001), and immature B cells (HR 0.26, 95%CI 0.12-0.59, p < 0.0001). In the METABRIC cohort (n = 236), activated B cells (HR 0.60, 95%CI 0.43-0.83, p = 0.002), and immature B cells (HR 0.65, 95%CI 0.47-0.91, p = 0.011). Cox regression suggested that immature B cells and activated B cells were protective factors for outcome OS.Aberrant activation of multiple pathways and low baseline tumor-infiltrating B cells are related to HER2 + BC trastuzumab-based recurrence, which primarily affects the antitumor activity of trastuzumab.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.