{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:46:59Z","timestamp":1782877619447,"version":"3.54.5"},"reference-count":41,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2022,4,17]],"date-time":"2022-04-17T00:00:00Z","timestamp":1650153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["#731105"],"award-info":[{"award-number":["#731105"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001593","name":"Irish Cancer Society","doi-asserted-by":"publisher","award":["CCRC13GAL"],"award-info":[{"award-number":["CCRC13GAL"]}],"id":[{"id":"10.13039\/501100001593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Backgorund<\/jats:title><jats:p>Prior data suggest pre\u2010diagnostic aspirin use impacts breast tumour biology and patient outcome. Here, we employed faithful surgical resection models of HER2+ and triple\u2010negative breast cancer (TNBC), to study outcome and response mechanisms across breast cancer subtypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>NOD\/SCID mice were implanted with HER2+ MDA\u2010MB\u2010231\/LN\/2\u20104\/H2N, trastuzumab\u2010resistant HER2+ HCC1954 or a TNBC patient\u2010derived xenograft (PDX). A daily low\u2010dose aspirin regimen commenced until primary tumours reached ~250\u2009mm<jats:sup>3<\/jats:sup> and subsequently resected. MDA\u2010MB\u2010231\/LN\/2\u20104\/H2N mice were monitored for metastasis utilising imaging. To interrogate the survival benefit of pre\u2010treatment aspirin, 3\u2009weeks post\u2010resection, HCC1954\/TNBC animals received standard\u2010of\u2010care (SOC) chemotherapy for 6\u2009weeks. Primary tumour response to aspirin was interrogated using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Aspirin delayed time to metastasis in MDA\u2010MB\u2010231\/LN\/2\u20104\/H2N xenografts and decreased growth of HER2<jats:sup>+<\/jats:sup>\/TNBC primary tumours. Lymphangiogenic factors and lymph vessels number were decreased in HER2<jats:sup>+<\/jats:sup> tumours. However, no survival benefit was seen in aspirin pre\u2010treated animals (HCC1954\/TNBC) that further received adjuvant SOC, compared with animals treated with SOC alone. In an effort to study mechanisms responsible for the observed reduction in lymphangiogenesis in HER2<jats:sup>+<\/jats:sup> BC we utilised an in vitro co\u2010culture system of HCC1954 tumour cells and mesenchymal stromal cells (MSC). Aspirin abrogated the secretion of VEGF\u2010C in MSCs and also decreased the lymph\/angiogenic potential of the MSCs and HCC1954 by tubule formation assay. Furthermore, aspirin decreased the secretion of uPA in HCC1954 cells potentially diminishing its metastatic capability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data employing clinically relevant models demonstrate that aspirin alters breast tumour biology. However, aspirin may not represent a robust chemo\u2010preventative agent in the HER2<jats:sup>+<\/jats:sup> or TNBC setting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4756","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T04:54:41Z","timestamp":1650257681000},"page":"3820-3836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Implementing subtype\u2010specific pre\u2010clinical models of breast cancer to study pre\u2010treatment aspirin effects"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6345","authenticated-orcid":false,"given":"Ian S.","family":"Miller","sequence":"first","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"},{"name":"National Preclinical Imaging Centre Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Khan","sequence":"additional","affiliation":[{"name":"Discipline of Surgery The Lambe Institute for Translational Research, National University of Ireland Galway  Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam P.","family":"Shiels","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudipto","family":"Das","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences Royal College of Surgeons in Ireland, St Stepehen's Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C.","family":"O' Farrell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Connor","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Lafferty","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Moran","sequence":"additional","affiliation":[{"name":"UCD School of Bimolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Isella","sequence":"additional","affiliation":[{"name":"Institute for Cancer Research and Treatment University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Loadman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, University of Bradford  Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emer","family":"Conroy","sequence":"additional","affiliation":[{"name":"UCD School of Bimolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Cohrs","sequence":"additional","affiliation":[{"name":"Center for Radiopharmaceutical Sciences Paul Scherrer Institute  Villigen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Schibli","sequence":"additional","affiliation":[{"name":"Center for Radiopharmaceutical Sciences Paul Scherrer Institute  Villigen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Kerbel","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute University of Toronto  Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"UCD School of Bimolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Marangoni","sequence":"additional","affiliation":[{"name":"Translational Research Department Institute Curie, PSL Research University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Bennett","sequence":"additional","affiliation":[{"name":"Division of Population Health Science Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darran P.","family":"O' Connor","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences Royal College of Surgeons in Ireland, St Stepehen's Green  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-0339","authenticated-orcid":false,"given":"R\u00f3is\u00edn M.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Discipline of Surgery The Lambe Institute for Translational Research, National University of Ireland Galway  Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette T.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Physiology and Medical Physics Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"},{"name":"National Preclinical Imaging Centre Royal College of Surgeons in Ireland, St Stephens Green  Dublin Ireland"},{"name":"UCD School of Bimolecular and Biomedical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.4"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210154"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-007-9641-5"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-011-1651-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2146"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2679"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23597"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1392"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.12.026"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2011.199"},{"key":"e_1_2_11_12_1","unstructured":"Institute NC.Provocative Questions \u2013 Identifying Perplexing Problems to Drive Progress Against Cancer. Available from:http:\/\/provocativequestions.nci.nih.gov."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2012.90"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018026161"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2014.05.007"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20110027"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4183"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45444-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp304"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl220"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6377"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10911-012-9266-0"},{"key":"e_1_2_11_24_1","volume-title":"Contribution: Angiogenesis Analyzer","author":"Carpentier G","year":"2012"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0078"},{"issue":"5","key":"e_1_2_11_26_1","first-page":"350","article-title":"Allred scoring for ER reporting and it's impact in clearly distinguishing ER negative from ER positive breast cancers","volume":"60","author":"Qureshi A","year":"2010","journal-title":"J Pak Med Assoc"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.39936"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-2400"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.123"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-018-1065-0"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13590"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2502"},{"issue":"5","key":"e_1_2_11_33_1","first-page":"1277","article-title":"Aspirin inhibits highly invasive prostate cancer cells","volume":"23","author":"Lloyd FP","year":"2003","journal-title":"Int J Oncol"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000464434"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-004-5783-x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2454"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2018.04.040"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.7918"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0230520"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-018-1020-5"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32083"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2016.12.008"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4756","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4756","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T05:35:31Z","timestamp":1692682531000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,17]]},"references-count":41,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/cam4.4756"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4756","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,17]]},"assertion":[{"value":"2021-07-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}