HER2/CEP17 ratio predicts residual cancer burden after neoadjuvant dual HER2 blockade: real-world data in patients with primary HER2-amplified breast cancer.
Myriam Stolz, Alex Farr, Kristina A Tendl-Schulz, Florian Frommlet, Helga Reckendorfer, Oskar Koperek, Barbara Neudert, Maximilian Marhold, Ulrike Heber, Ruth Exner, Christian F Singer, Rupert Bartsch, Zsuzsanna Bago-Horvath
{"title":"HER2/CEP17 ratio predicts residual cancer burden after neoadjuvant dual HER2 blockade: real-world data in patients with primary HER2-amplified breast cancer.","authors":"Myriam Stolz, Alex Farr, Kristina A Tendl-Schulz, Florian Frommlet, Helga Reckendorfer, Oskar Koperek, Barbara Neudert, Maximilian Marhold, Ulrike Heber, Ruth Exner, Christian F Singer, Rupert Bartsch, Zsuzsanna Bago-Horvath","doi":"10.1007/s00428-025-04203-5","DOIUrl":null,"url":null,"abstract":"<p><p>Novel human epidermal growth factor receptor 2 (HER2)-directed therapies have significantly improved outcomes for patients with HER2-positive early-stage breast cancer. Our study assessed the impact of HER2/chromosome enumeration probe 17 (CEP17) ratio on residual cancer burden (RCB) and long-term prognosis following neoadjuvant chemotherapy with dual HER2-targeted therapy using trastuzumab and pertuzumab to identify candidates for chemotherapy de-escalation. Our study included 169 patients with primary invasive HER2-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab and pertuzumab at the Medical University of Vienna from 2014 to 2020. HER2 (ERBB2) gene copy number and HER2/CEP17 ratio were assessed by in situ hybridization. RCB and pathologic complete remission (pCR) served as primary and secondary endpoints, respectively. Univariate and multivariate logistic regression models were applied to analyze associations between outcomes and predictor variables, focusing on the predictive role of HER2/CEP17 ratio, with cutoff values estimated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. HER2/CEP17 ratio was significantly associated with response to dual-targeted neoadjuvant chemotherapy in primary HER2-positive breast cancer. Optimal HER2/CEP17 cutoff for predicting RCB 0/I was identified at 5.19. HER2/CEP17 ratio was also significantly associated with PFS as a continuous predictor. Multivariate analysis showed that hormone receptor status and the presence of an in situ tumor component significantly influenced therapy response. HER2/CEP17 ratio predicts therapy response and therefore might aid patient stratification for therapy de-escalation with respect to dual neoadjuvant HER2 blockade. Further investigations are warranted to confirm its relevance with other HER2-targeted agents.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-025-04203-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Novel human epidermal growth factor receptor 2 (HER2)-directed therapies have significantly improved outcomes for patients with HER2-positive early-stage breast cancer. Our study assessed the impact of HER2/chromosome enumeration probe 17 (CEP17) ratio on residual cancer burden (RCB) and long-term prognosis following neoadjuvant chemotherapy with dual HER2-targeted therapy using trastuzumab and pertuzumab to identify candidates for chemotherapy de-escalation. Our study included 169 patients with primary invasive HER2-positive breast cancer who received neoadjuvant chemotherapy with trastuzumab and pertuzumab at the Medical University of Vienna from 2014 to 2020. HER2 (ERBB2) gene copy number and HER2/CEP17 ratio were assessed by in situ hybridization. RCB and pathologic complete remission (pCR) served as primary and secondary endpoints, respectively. Univariate and multivariate logistic regression models were applied to analyze associations between outcomes and predictor variables, focusing on the predictive role of HER2/CEP17 ratio, with cutoff values estimated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. HER2/CEP17 ratio was significantly associated with response to dual-targeted neoadjuvant chemotherapy in primary HER2-positive breast cancer. Optimal HER2/CEP17 cutoff for predicting RCB 0/I was identified at 5.19. HER2/CEP17 ratio was also significantly associated with PFS as a continuous predictor. Multivariate analysis showed that hormone receptor status and the presence of an in situ tumor component significantly influenced therapy response. HER2/CEP17 ratio predicts therapy response and therefore might aid patient stratification for therapy de-escalation with respect to dual neoadjuvant HER2 blockade. Further investigations are warranted to confirm its relevance with other HER2-targeted agents.
期刊介绍：
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
