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Used as monotherapy or with trastuzumab, capecitabine, and paclitaxel, it is evaluated across neoadjuvant, adjuvant, and metastatic settings, especially CNS metastasis, for longer adjuvant benefit and recurrence risk reduction.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/neratinib-for-her2-positive-breast-cancer-with-an-overlooked-option/381732/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/neratinib-for-her2-positive-breast-cancer-with-an-overlooked-option/381732.png","ImageObject",300,407,{"name":42,"@type":43},"eBook King","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is neratinib relevant for HER2-positive breast cancer?","Question",{"text":63,"@type":64},"Neratinib inhibits HER1/HER2/HER4 signaling, providing anticancer activity. 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Molecular Medicine (2023) 29:134 Molecular Medicine  \n[https://doi.org/10.1186/s10020-023-00736-0](https://doi.org/10.1186/s10020-023-00736-0)  \nREVIEW Open Access  \nNeratinib for HER2-positive breast cancer with an overlooked option  \nLiting Guo 1*†, Weiwei Shao2†, Chenfei Zhou 1, Hui Yang 1, Liu Yang 1, Qu Cai 1, Junqing Wang3*, Yan Shi4*, Lei Huang 1,5* and Jun Zhang 1  \nAbstract  \nPositive human epidermal growth factor receptor 2 (HER2) expression is associated with an increased risk of metastases especially those to the brain in patients with advanced breast cancer (BC) . Neratinib as a tyrosine kinase inhibitor can prevent the transduction of HER1, HER2 and HER4 signaling pathways thus playing an anticancer effect. Moreover, neratinib has a certain efficacy to reverse drug resistance in patients with BC with previous HER2 monoclonal antibody or targeted drug resistance. Neratinib, as monotherapy and in combination with other therapies, has been tested in the neoadjuvant, adjuvant, and metastatic settings. Neratinib with high anticancer activity is indicated for the prolonged adjuvant treatment of HER2-positive early BC, or in combination with other drugs including trastuzumab, capecitabine, and paclitaxel for the treatment of advanced HER2-positive BC especially cancers with central nervous system (CNS) metastasis to reduce the risk of BC recurrence. This article reviewed the pharmacological profiles, efficacy, safety, tolerability, and current clinical trials pertaining to neratinib, with a particular focus on the use of neratinib in patients with metastatic breast cancer (MBC) involving the CNS. We further discussed the use of neratinib for HER2-negative and HER2-mutant breast cancers, and mechanisms of resistance to neratinib. The current evidence suggests that neratinib has promising efficacy in patients with BC which is at least non-inferior compared to previous therapeutic regimens. The most common AE was diarrhea, and the incidence, severity and duration of neratinib-related grade 3 diarrhea can be reduced with loperamide. Of note, neratinib has the potential to effectively control and prevent brain metastasis in patients with advanced BC, providing a therapeutic strategy for HER2-positive BC.  \nKeywords Neratinib, Breast cancer, HER2, Central nervous system metastasis  \n†Liting Guo and Weiwei Shao contributed equally to this work.  \n*Correspondence: Liting Guo[gltonline@163.com](gltonline@163.com)  \nJunqing Wang [wangjunqingmd@hotmail.com](wangjunqingmd@hotmail.com)[ ](wangjunqingmd@hotmail.com)Yan Shi  \n[sy_rjh@aliyun.com](sy_rjh@aliyun.com)[ ](sy_rjh@aliyun.com)Lei Huang [lei.huang@alumni.dkfz.de](lei.huang@alumni.dkfz.de)  \n1Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 2Department of Pathology, The First People’s Hospital of Yancheng City, Yancheng, China  \n3Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 4Department of General Surgery, Shanghai Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, 358 Datong Road, Gaoqiao Town, Shanghai 200137, China  \n5Medical Center on Aging of Ruijin Hospital, MCARJH, Shanghai Jiaotong University School of Medicine, Shanghai, China  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your i","cbCaidGMWb7q4QoV","https://ap.wps.com/l/cbCaidGMWb7q4QoV","pdf",1950520,23,"English","# Abstract\n# Background\n## HER2 expression and metastatic risk\n## CNS involvement and burden of breast cancer brain metastasis\n## Treatment goals and multidisciplinary management\n## Barriers to drug delivery in the CNS","[{\"question\":\"Why is neratinib relevant for HER2-positive breast cancer?\",\"answer\":\"Neratinib inhibits HER1/HER2/HER4 signaling, providing anticancer activity. It also shows efficacy in reversing drug resistance after prior HER2-targeted treatments.\"},{\"question\":\"How has neratinib been tested across treatment settings?\",\"answer\":\"It has been studied as monotherapy and in combination therapies in neoadjuvant, adjuvant, and metastatic contexts, including regimens with trastuzumab, capecitabine, and paclitaxel.\"},{\"question\":\"What adverse event is most common with neratinib?\",\"answer\":\"Diarrhea is reported as the most common adverse event. Loperamide can reduce the incidence, severity, and duration of grade 3 neratinib-related diarrhea.\"}]","Neratinib for HER2-positive breast cancer with an overlooked option | PDF",1790246762,58]