{"title":"Narrative review on the evolving role of HER2/neu targeting in uterine serous cancers.","authors":"Aarthi S Jayraj, Salamatu Abdul-Aziz, Anisa Mburu, Avinash Upadhyay, Nilanchali Singh, Prafull Ghatage","doi":"10.21037/atm-23-1465","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Serous endometrial cancers (ECs) are an aggressive histotype of ECs which are disproportionately responsible for 40% of cancer-specific mortality rates despite constituting only 5-10% of all uterine cancers in incidence. In recent times, it has become increasingly evident that about 20-40% of uterine serous cancers (USCs) have molecular alterations in <i>ERBB2</i> pathway with human epidermal growth factor receptor 2 (HER2/neu) amplification or overexpression. We summarise the evidence on genetic and molecular alterations in HER2/neu pathway in USC with a focus on testing criteria, targeting agents and resistance mechanisms.</p><p><strong>Methods: </strong>We conducted a database search of PubMed/Medline up to 28th February 2023 for articles published in the English language using pre-defined search terms. One hundred and seventy-one relevant articles were subsequently reviewed for eligibility and inclusion in the review.</p><p><strong>Key content and findings: </strong>The Cancer Genome Atlas (TCGA) classification is a significant development in the molecular profiling of ECs with a positive impact on the treatment of these tumors including USCs. Testing criteria for HER2/neu in USC with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has evolved in more than a decade with progress made towards EC specific testing guidelines. The findings of a recent phase III study have led to the development of practice changing guidelines towards improving patient outcomes.</p><p><strong>Conclusions: </strong>Molecular aberration in the HER2/neu pathway contributes to the aggressive behaviour of USC. Considering the clinical benefit conferred by HER2/neu targeted therapy, HER2/neu testing is recommended for all cases of serous EC in advanced and recurrent settings. Trastuzumab in combination with platinum and taxanes based chemotherapy is the recommended treatment option for patients with advanced or recurrent serous cancers who test positive to HER2/neu. Clinical trials on targeted therapy are ongoing and future research should focus on selection of patients who will derive the most benefit from such therapy.</p>","PeriodicalId":8216,"journal":{"name":"Annals of translational medicine","volume":"12 4","pages":"69"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304437/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of translational medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/atm-23-1465","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/9 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background and objective: Serous endometrial cancers (ECs) are an aggressive histotype of ECs which are disproportionately responsible for 40% of cancer-specific mortality rates despite constituting only 5-10% of all uterine cancers in incidence. In recent times, it has become increasingly evident that about 20-40% of uterine serous cancers (USCs) have molecular alterations in ERBB2 pathway with human epidermal growth factor receptor 2 (HER2/neu) amplification or overexpression. We summarise the evidence on genetic and molecular alterations in HER2/neu pathway in USC with a focus on testing criteria, targeting agents and resistance mechanisms.
Methods: We conducted a database search of PubMed/Medline up to 28th February 2023 for articles published in the English language using pre-defined search terms. One hundred and seventy-one relevant articles were subsequently reviewed for eligibility and inclusion in the review.
Key content and findings: The Cancer Genome Atlas (TCGA) classification is a significant development in the molecular profiling of ECs with a positive impact on the treatment of these tumors including USCs. Testing criteria for HER2/neu in USC with immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has evolved in more than a decade with progress made towards EC specific testing guidelines. The findings of a recent phase III study have led to the development of practice changing guidelines towards improving patient outcomes.
Conclusions: Molecular aberration in the HER2/neu pathway contributes to the aggressive behaviour of USC. Considering the clinical benefit conferred by HER2/neu targeted therapy, HER2/neu testing is recommended for all cases of serous EC in advanced and recurrent settings. Trastuzumab in combination with platinum and taxanes based chemotherapy is the recommended treatment option for patients with advanced or recurrent serous cancers who test positive to HER2/neu. Clinical trials on targeted therapy are ongoing and future research should focus on selection of patients who will derive the most benefit from such therapy.
期刊介绍：
The Annals of Translational Medicine (Ann Transl Med; ATM; Print ISSN 2305-5839; Online ISSN 2305-5847) is an international, peer-reviewed Open Access journal featuring original and observational investigations in the broad fields of laboratory, clinical, and public health research, aiming to provide practical up-to-date information in significant research from all subspecialties of medicine and to broaden the readers’ vision and horizon from bench to bed and bed to bench. It is published quarterly (April 2013- Dec. 2013), monthly (Jan. 2014 - Feb. 2015), biweekly (March 2015-) and openly distributed worldwide. Annals of Translational Medicine is indexed in PubMed in Sept 2014 and in SCIE in 2018. Specific areas of interest include, but not limited to, multimodality therapy, epidemiology, biomarkers, imaging, biology, pathology, and technical advances related to medicine. Submissions describing preclinical research with potential for application to human disease, and studies describing research obtained from preliminary human experimentation with potential to further the understanding of biological mechanism underlying disease are encouraged. Also warmly welcome are studies describing public health research pertinent to clinic, disease diagnosis and prevention, or healthcare policy. With a focus on interdisciplinary academic cooperation, ATM aims to expedite the translation of scientific discovery into new or improved standards of management and health outcomes practice.
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