Exploring immune activation patterns in HER2-low and HER2-ultralow breast cancer subtypes.

IF 4.8 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-06-04 DOI:10.1093/oncolo/oyaf081

Gyöngyi Munkácsy, Libero Santarpia, Balázs Győrffy

{"title":"Exploring immune activation patterns in HER2-low and HER2-ultralow breast cancer subtypes.","authors":"Gyöngyi Munkácsy, Libero Santarpia, Balázs Győrffy","doi":"10.1093/oncolo/oyaf081","DOIUrl":null,"url":null,"abstract":"Background: A deeper understanding of the molecular and clinical characteristics of HER2-low and ultralow breast cancer (BC) subtypes is essential for advancing therapeutic strategies.Methods: Three independent GEO datasets with microarray and IHC/FISH data from 510 BC patients were analyzed to establish reliable HER2 expression cutoff values (>3034 for HER2-positivity and <1780 for HER2-ultralow), defining HER2-positive (HER2+), HER2-low, and HER2-ultralow cohorts. Combined with hormone receptor status, six distinct BC subgroups were identified. Prognosis was evaluated using univariate and multivariate survival analysis in a dataset of 7830 BC patients, alongside correlative analysis of 17 immune-related gene signatures across subgroups. A PubMed literature review compared our findings with existing studies.Results: In hormone receptor-positive (HR+) patients, HER2-low tumors were associated with better prognosis than HER2-ultralow and HER2+ subgroups (P = .0048 for relapse-free survival (RFS) and P = .0015 for distant-metastasis-free survival (DMFS)). No prognostic significance was observed in HR-negative (HR-) patients. Immune gene activation was consistently higher in HR- tumors, with HER2-low (HR+ and HR-) and HR-/HER2+ patients showing significant immune signature overlap. While HR+/HER2-ultralow and HR+/HER2+ patients had modest immune activation, HR-/HER2-ultralow patients exhibited the strongest association with immune signaling, including IFN signaling, T cell-activating cytokines, and cytotoxic effector molecules.Conclusions: These findings, supported by a comprehensive literature review, indicate that patients with HER2-low and HER2-ultralow BC exhibit distinct immune patterns, which supports their classification as unique BC subgroups.","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 6","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205994/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncologist","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/oncolo/oyaf081","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: A deeper understanding of the molecular and clinical characteristics of HER2-low and ultralow breast cancer (BC) subtypes is essential for advancing therapeutic strategies.

Methods: Three independent GEO datasets with microarray and IHC/FISH data from 510 BC patients were analyzed to establish reliable HER2 expression cutoff values (>3034 for HER2-positivity and <1780 for HER2-ultralow), defining HER2-positive (HER2+), HER2-low, and HER2-ultralow cohorts. Combined with hormone receptor status, six distinct BC subgroups were identified. Prognosis was evaluated using univariate and multivariate survival analysis in a dataset of 7830 BC patients, alongside correlative analysis of 17 immune-related gene signatures across subgroups. A PubMed literature review compared our findings with existing studies.

Results: In hormone receptor-positive (HR+) patients, HER2-low tumors were associated with better prognosis than HER2-ultralow and HER2+ subgroups (P = .0048 for relapse-free survival (RFS) and P = .0015 for distant-metastasis-free survival (DMFS)). No prognostic significance was observed in HR-negative (HR-) patients. Immune gene activation was consistently higher in HR- tumors, with HER2-low (HR+ and HR-) and HR-/HER2+ patients showing significant immune signature overlap. While HR+/HER2-ultralow and HR+/HER2+ patients had modest immune activation, HR-/HER2-ultralow patients exhibited the strongest association with immune signaling, including IFN signaling, T cell-activating cytokines, and cytotoxic effector molecules.

Conclusions: These findings, supported by a comprehensive literature review, indicate that patients with HER2-low and HER2-ultralow BC exhibit distinct immune patterns, which supports their classification as unique BC subgroups.

查看原文本刊更多论文

探索低her2和超低her2乳腺癌亚型的免疫激活模式。

背景：深入了解her2低和超低乳腺癌（BC）亚型的分子和临床特征对于推进治疗策略至关重要。方法：分析来自510例BC患者的三个独立的GEO数据集，包括微阵列和IHC/FISH数据，以建立可靠的HER2表达临界值（HER2阳性为>3034）。结果：在激素受体阳性（HR+）患者中，HER2低肿瘤比HER2超低和HER2+亚组预后更好(P =；0048无复发生存期（RFS）， P =。0015的远端无转移生存期（DMFS）)。HR阴性（HR-）患者无预后意义。免疫基因激活在HR-肿瘤中始终较高，HER2-低（HR+和HR-）和HR-/HER2+患者表现出明显的免疫特征重叠。虽然HR+/HER2-超低和HR+/HER2+患者有适度的免疫激活，但HR-/HER2-超低患者表现出与免疫信号的最强关联，包括IFN信号、T细胞激活因子和细胞毒性效应分子。结论：综合文献综述支持这些发现，表明her2低和her2超低的BC患者表现出不同的免疫模式，这支持了他们作为独特的BC亚群的分类。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.