{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:18Z","timestamp":1789409598309,"version":"build-2803163510"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":42,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["U10CA180821"],"award-info":[{"award-number":["U10CA180821"]}]},{"name":"National Cancer Institute","award":["U24CA176171"],"award-info":[{"award-number":["U24CA176171"]}]},{"name":"National Cancer Institute","award":["UG1CA233373"],"award-info":[{"award-number":["UG1CA233373"]}]},{"name":"National Cancer Institute","award":["P50-CA058223"],"award-info":[{"award-number":["P50-CA058223"]}]},{"name":"Susan G. Komen","award":["SAC-160074"],"award-info":[{"award-number":["SAC-160074"]}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"crossref","award":["BCRF-23-127"],"award-info":[{"award-number":["BCRF-23-127"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["R01-CA229409"],"award-info":[{"award-number":["R01-CA229409"]}]},{"name":"UNC LCCC Triple Negative Breast Cancer Center","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Despite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>To better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II\/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Our study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>RD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT00861705.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>NIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci205962","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:01:14Z","timestamp":1785859274000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance)"],"prefix":"10.1172","volume":"136","author":[{"given":"Patrick D.","family":"R\u00e4dler","sequence":"first","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke M.","family":"Felsheim","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"},{"name":"Bioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel Hill (UNC), Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aranzazu","family":"Fernandez-Martinez","sequence":"additional","affiliation":[{"name":"Drug Development Department (DITEP), INSERM UMR981, IHU-National PRecISion Medicine Center in Oncology, Gustave Roussy Cancer Campus, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Pfefferle","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"},{"name":"Department of Genetics, UNC, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele C.","family":"Hayward","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baljit","family":"Singh","sequence":"additional","affiliation":[{"name":"White Plains Hospital, White Plains, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Sikov","sequence":"additional","affiliation":[{"name":"Program in Women\u2019s Oncology, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-4649","authenticated-orcid":true,"given":"Lisa A.","family":"Carey","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"},{"name":"Division of Hematology-Oncology, Department of Medicine, School of Medicine, UNC, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-2247","authenticated-orcid":true,"given":"Charles M.","family":"Perou","sequence":"additional","affiliation":[{"name":"Lineberger Comprehensive Cancer Center (LCCC) and"},{"name":"Department of Genetics, UNC, Chapel Hill, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3492"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00468-0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910549"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2112651"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2409932"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_390464"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612645"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz208"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2010.11.003"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15081"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30904-X"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26502-6"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0432"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01506"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.10.012"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31953-X"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.102855"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.09.003"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0286"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.041"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.012"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.02.002"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.0572"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-025-00740-z"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4137\/CIN.S9983"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157368"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.10.6823"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.1010"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.06.049"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31238-y"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13588-2"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1640-4"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105043"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113342"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130323"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nature08989"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14864"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31764-9"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-021-00312-w"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11071037"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03351-7"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aar3451"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000303"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2028485"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2203690"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.1.180"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6477"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.03.003"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.033"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02309"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-4-3"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.01276"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.1370"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.08.022"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0611-3"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/205962\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:02:01Z","timestamp":1789408921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/205962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":55,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,6,30]]},"published-print":{"date-parts":[[2026,9,15]]}},"alternative-id":["10.1172\/JCI205962"],"URL":"https:\/\/doi.org\/10.1172\/jci205962","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"article-number":"e205962"}}