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In primary breast cancers it correlated with higher tumor grades, aggressive subtypes, and worse 5-year survival, and in brain metastases it was frequently detected, up to about 90%, with variability across primary tumor types.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},331991,1790144175,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Article  \nB7-H3 Expression in Breast Cancer and Brain Metastasis  \nVaibhavi Joshi 1, Kate Beecher 1, Malcolm Lim 1, Andrew Stacey 1, Yufan Feng 1, Parmjit S. Jat 2, Pascal H. G. Duijf 3, Peter T. Simpson 1, Sunil R. Lakhani 1,4, * and Amy E. McCart Reed 1, *  \nCitation: Joshi, V.; Beecher, K.; Lim, M.; Stacey, A.; Feng, Y.; Jat, P.S.; Duijf, P.H.G.; Simpson, P.T.; Lakhani, S.R.; McCart Reed, A.E. B7-H3 Expression in Breast Cancer and Brain Metastasis. Int. J. Mol. Sci. 2024, 25, 3976. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25073976  \nAcademic Editors: Nicoletta Cordani and Monica Iorfida  \nReceived: 27 February 2024  \nRevised: 22 March 2024  \nAccepted: 27 March 2024  \nPublished: 3 April 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane 4029, Australia; [vaibhavi.joshi@uq.edu.au](vaibhavi.joshi@uq.edu.au) (V.J.); [kate.matthews@uq.edu.au](kate.matthews@uq.edu.au) (K.B.); [malcolm.lim@uq.edu.au](malcolm.lim@uq.edu.au) (M.L.); [andrew.stacey@health.qld.gov.au](andrew.stacey@health.qld.gov.au) (A.S.); [yufan.feng@uq.edu.au](yufan.feng@uq.edu.au) (Y.F.); [p.simpson@uq.edu.au](p.simpson@uq.edu.au) (P.T.S.)  \n2 MRC Prion Unit at UCL, Institute of Prion Diseases, Courtauld Building, London W1W 7FF, UK; [p.jat@prion.ucl.ac.uk](p.jat@prion.ucl.ac.uk)  \n3 Centre for Cancer Biology, Clinical and Health Sciences, University of South Australia & SA Pathology, Adelaide 5001, Australia; [pascal.duijf@unisa.edu.au](pascal.duijf@unisa.edu.au)  \n4 Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia  \n* Correspondence: [s.lakhani@uq.edu.au](s.lakhani@uq.edu.au) (S.R.L.); [amy.reed@uq.edu.au](amy.reed@uq.edu.au) (A.E.M.R.)  \nAbstract: Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137) . In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancerspecific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3 . However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively) . The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management.  \nKeywords: breast cancer; brain metasta","cbCaifbqOcIxXN5u","https://ap.wps.com/l/cbCaifbqOcIxXN5u","pdf",5157326,17,"English","# Abstract\n# Introduction\n## Clinical context and treatment challenges\n## B7-H3 (CD276) background and immunological role","[{\"question\":\"Why is brain metastasis a major problem in some breast cancer patients?\",\"answer\":\"Brain metastasis is aggressive, has limited treatment options, and leads to poor clinical outcomes.\"},{\"question\":\"What is B7-H3 (CD276) and why is it relevant to therapy?\",\"answer\":\"B7-H3 is an immune checkpoint molecule involved in T-cell suppression and has been linked to poor survival, making it a potential interventional target.\"},{\"question\":\"How was B7-H3 expression measured, and what did the study find in primary tumors and brain metastases?\",\"answer\":\"B7-H3 was assessed by immunohistochemistry on tissue microarrays from three cohorts. In primary breast cancers it correlated with higher tumor grades, aggressive subtypes, and worse 5-year survival, and in brain metastases it was frequently detected, up to about 90%, with variability across primary tumor types.\"}]","B7-H3 Expression in Breast Cancer and Brain Metastasis | PDF",1789996196,43]