{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:09:27Z","timestamp":1781284167436,"version":"3.54.1"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Advanced Technology Genomics Core","award":["CA016672"],"award-info":[{"award-number":["CA016672"]}]},{"name":"Advanced Technology Genomics Core","award":["Moon Shots Program, The University of Texas MD And"],"award-info":[{"award-number":["Moon Shots Program, The University of Texas MD And"]}]},{"name":"Advanced Technology Genomics Core","award":["Puma Biotechnology Investigator Initiated Study Pr"],"award-info":[{"award-number":["Puma Biotechnology Investigator Initiated Study Pr"]}]},{"name":"Advanced Technology Genomics Core","award":["State of Texas Grant for Rare and Aggressive Breas"],"award-info":[{"award-number":["State of Texas Grant for Rare and Aggressive Breas"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Inflammatory breast cancer (IBC) is rare but aggressive, characterized by the rapid onset of diffuse skin erythema, edema, tenderness, induration, and fast metastasis. Both hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+) are associated with inferior response after neoadjuvant systemic therapy (NAST) compared to non-IBC. Despite multimodal treatment approaches, the 3-year overall survival rate for stage III IBC remains low at approximately 74%, around 10% lower than the 83% for non-IBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate whether the addition of neratinib, an irreversible pan-ErbB receptor small molecule tyrosine kinase inhibitor, improves the rate of pathological complete response in both HER2+ and HR+\/HER2\u2212 IBC in neoadjuvant therapy, and to assess safety and explore biomarkers associated with response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>This is a phase I\/II (HER2+; cohort 1) and II (HR+\/HER2\u2212; cohort II trial conducted at a single center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Pathological response was assessed using the pathological complete response (pCR) and residual cancer burden (RCB) criteria as the primary efficacy endpoint. Safety and biomarkers were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In cohort 1, dose-limiting toxicities were Grade 2\/3 diarrhea. Among the 10 evaluable patients from cohort 1 who underwent surgery, 5 achieved pCR (50%); in the intention-to-treat population of all 14 patients (counting drop-outs as nonresponders), the pCR rate was 36%. In cohort 2, 16 patients were enrolled, and 1 (6%) achieved pCR. Common adverse events (AEs) included Grade 2 alopecia, Grade 2\/3 diarrhea, anemia, nausea, and neutropenia. High toxicity led to early closure of accrual. The median event-free survival in cohort 2 was 27.5 months, and was not reached for cohort 1 by data cutoff. Biomarker analysis showed that good responders (pCR + RCB-I) in both cohorts exhibited upregulation of immune-activating pathways, including interferon signaling and cytotoxic T-cell markers. By contrast, poor responders (RCB-II + RCB-III) showed immune-suppressive features, increased angiogenesis, proliferation, and anti-apoptotic gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The addition of neratinib to neoadjuvant therapy showed potential in improving the pCR rate in HER2+ IBC (36% in this study) but not in HR+\/HER2\u2212 (6%), though high toxicity was a major limiting factor. Further research is needed to optimize the balance between efficacy and safety. Biomarker analysis uncovered interesting new hypothesis-generating data warranting future study in IBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT03101748.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359251379392","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:04:20Z","timestamp":1760450660000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["A phase Ib\/II trial of neoadjuvant neratinib added to standard therapy in patients with HER2-positive or HR-positive\/HER2-negative inflammatory breast cancer (including stage III and IV disease)"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-6058","authenticated-orcid":false,"given":"Bora","family":"Lim","sequence":"first","affiliation":[{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 1354, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Roland","family":"Bassett","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Willey","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-9342","authenticated-orcid":false,"given":"Azadeh","family":"Nasrazadani","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad M.","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Advanced Genomics Technology Core (AGTC), The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Advanced Genomics Technology Core (AGTC), The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-174X","authenticated-orcid":false,"given":"Anthony","family":"Lucci","sequence":"additional","affiliation":[{"name":"Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie X.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Stauder","sequence":"additional","affiliation":[{"name":"Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Whitman","sequence":"additional","affiliation":[{"name":"Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huong","family":"Le-Petross","sequence":"additional","affiliation":[{"name":"Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Valero","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"MDACC Inflammatory Breast Cancer Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Woodward","sequence":"additional","affiliation":[{"name":"Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M.","family":"Layman","sequence":"additional","affiliation":[{"name":"The Morgan Welch Inflammatory Breast Cancer Clinic and Research Program, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 1354, Houston, TX 77030, USA"},{"name":"Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20082"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.suc.2018.03.009"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0010-y"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145534"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.8-2-141"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050664"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22927"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2024-4852"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-020-09392-8"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.1436"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-015-3691-4"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-015-3592-z"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt525"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12162"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.1002"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2017.1299707"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0237"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1148"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00551-3"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0349"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-017-4165-0"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(89)90015-9"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.05.012"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100722"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720012310038"},{"key":"e_1_3_4_30_2","unstructured":"Aleksander SA Balhoff J Carbon S et al. The gene ontology knowledgebase in 2023. Genetics 2023; 224: iyad031. https:\/\/pubmed.ncbi.nlm.nih.gov\/36866529\/"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2018.07.008"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.35.15_suppl.580"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1413513"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt182"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2013-0217"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113216"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.23969"}],"container-title":["Therapeutic Advances in Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359251379392","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17588359251379392","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17588359251379392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:33:24Z","timestamp":1777588404000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17588359251379392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":36,"alternative-id":["10.1177\/17588359251379392"],"URL":"https:\/\/doi.org\/10.1177\/17588359251379392","relation":{},"ISSN":["1758-8359","1758-8359"],"issn-type":[{"value":"1758-8359","type":"print"},{"value":"1758-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"article-number":"17588359251379392"}}