Xu Chi, Wang Yahui, Hong Yuanyuan, Yao Ru, Wu Lijia, Shen Xi, Qu Yang, Zhang Zhuo, Zhu Wei, Yang Ying, Chen Weizhi, Zhou Yidong, Liang Zhiyong
Department of Breast Surgery, Peking Union Medical College Hospital, Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Genecast Biotechnology Co., Ltd, Wuxi, Jiangsu, China.
Breast Cancer Res Treat. 2023 Jun;199(3):603-615. doi: 10.1007/s10549-023-06931-1. Epub 2023 Apr 21.
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.
确定与基于曲妥珠单抗治疗的人表皮生长因子受体2阳性（HER2+）乳腺癌（BC）复发相关的遗传和免疫特征。
一项对48例接受基于曲妥珠单抗治疗的患者的回顾性队列研究，根据临床随访分为复发组和非复发组。对所有48例患者的基线样本进行基因变异、HLA等位基因类型、基因表达和免疫特征分析，这些与HER2+ BC复发相关。统计方法包括逻辑回归模型、Kaplan-Meier曲线和单变量Cox比例风险模型。
与非复发组相比，复发组中细胞外基质相关通路和3个标志性基因集富集。非复发组中未成熟B细胞和活化B细胞的浸润水平显著增加，这在另外两个已发表的基因表达数据集（包括TCGA和METABRIC）中与总体生存期（OS）的改善显著相关。在TCGA队列（n = 275）中，活化B细胞（HR 0.23，95%CI 0.13 - 0.43，p < 0.0001）和未成熟B细胞（HR 0.26，95%CI 0.12 - 0.59，p < 0.0001）。在METABRIC队列（n = 236）中，活化B细胞（HR 0.60，95%CI 0.43 - 0.83，p = 0.002）和未成熟B细胞（HR 0.65，95%CI 0.47 - 0.91，p = 0.011）。Cox回归表明未成熟B细胞和活化B细胞是OS结局的保护因素。
多种通路的异常激活和低基线肿瘤浸润B细胞与基于曲妥珠单抗的HER2+ BC复发相关，这主要影响曲妥珠单抗的抗肿瘤活性。
