{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:25:28Z","timestamp":1791487528782,"version":"4.3.4"},"reference-count":11,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"\n Importance<\/jats:title>\n \n The neoadjuvant combination of paclitaxel, trastuzumab, and pertuzumab (THP) represents a promising abbreviated regimen for early-stage\n ERBB2<\/jats:italic>\n -positive breast cancer, but long-term outcomes and the role of ultrasensitive circulating tumor DNA (ctDNA) monitoring remain incompletely defined.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To assess 5-year outcomes and characterize ctDNA dynamics with an ultrasensitive assay in patients with\n ERBB2<\/jats:italic>\n -positive breast cancer receiving neoadjuvant THP.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n \n This study was a prespecified secondary analysis of the prospective, single-arm, investigator-initiated phase 2 DAPHNe nonrandomized clinical trial. Patients were enrolled in the DAPHNe trial from November 2018 to January 2020. The trial took place at a multicenter academic cancer center and affiliated community practices. Participants included patients with stage II to III\n ERBB2<\/jats:italic>\n -positive breast cancer receiving neoadjuvant THP for 12 weeks. Ultrasensitive ctDNA analyses were performed in patients with available tumor tissue and serial plasma samples. The secondary analysis was conducted between between March 2023 and April 2025.\n <\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Neoadjuvant THP administered for 12 weeks, followed by surgery and adjuvant therapy guided by pathologic response.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Main outcomes included 5-year event-free survival, recurrence-free interval (RFI), distant RFI, and overall survival. ctDNA detection and clearance were assessed using a whole-genome\u2013based, tumor-informed ultrasensitive assay at 4 predefined time points (baseline, preoperative, postoperative, and late adjuvant).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The overall trial cohort included 98 patients (median [IQR] age, 49.5 years [24.0-78.0 years]; 97 female patients [99.0%]; 1 male patient [1.0%]), with mostly stage 2 disease (91 patients [92.9%]) and hormone receptor\u2013positive tumors (65 patients [66.3%]). With a median (IQR) follow-up of 5.2 (5.0-5.4) years, the 5-year event-free survival was 99% (95% CI, 97%-100%), the 5-year RFI was 98% (95% CI, 93%-100%), the 5-year distant RFI was 100% (95% CI, 100%-100%), and the 5-year overall survival was 99% (95% CI, 97%-100%). Among 57 patients included in ctDNA analyses, baseline ctDNA was detected in 51 individuals (89.5%). After neoadjuvant therapy, ctDNA clearance occurred in 49 of 51 patients (96.1%), with only 2 individuals (3.9%) remaining ctDNA-positive preoperatively; detectability remained low (&amp;lt;10%) during postoperative follow-up. One single patient experienced a local recurrence, with ctDNA detected at time of recurrence and cleared following surgical resection.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this secondary analysis of the DAPHNe nonrandomized clinical trial, neoadjuvant THP was associated with excellent long-term outcomes in patients with early-stage\n ERBB2<\/jats:italic>\n -positive breast cancer. Ultrasensitive ctDNA analyses demonstrated high baseline detection rates and near-universal clearance after abbreviated neoadjuvant therapy, supporting further investigation of ctDNA-guided de-escalation strategies in this setting.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03716180<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.2023","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:30:32Z","timestamp":1782401432000},"page":"868","source":"Crossref","is-referenced-by-count":3,"title":["Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab for Stage II to III,\n ERBB2<\/i>\n -Positive Breast Cancer"],"prefix":"10.1001","volume":"12","author":[{"given":"Paolo","family":"Tarantino","sequence":"first","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer 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Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashka","family":"Patel","sequence":"additional","affiliation":[{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"El-Refai","sequence":"additional","affiliation":[{"name":"Personalis Inc., Fremont, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Abbott","sequence":"additional","affiliation":[{"name":"Personalis Inc., Fremont, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailiang","family":"Li","sequence":"additional","affiliation":[{"name":"Personalis Inc., Fremont, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Personalis Inc., Fremont, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O.","family":"Chen","sequence":"additional","affiliation":[{"name":"Personalis Inc., Fremont, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam V.","family":"Desai","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Spring","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine M.","family":"Tung","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Faggen","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Constantine","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tari A.","family":"King","sequence":"additional","affiliation":[{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Breast Surgery, Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian E.","family":"Krop","sequence":"additional","affiliation":[{"name":"Yale Cancer Center, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabihah","family":"Tayob","sequence":"additional","affiliation":[{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Mittendorf","sequence":"additional","affiliation":[{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Breast Surgery, Department of Surgery, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Tolaney","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Winer","sequence":"additional","affiliation":[{"name":"Yale Cancer Center, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Broad Institute of Harvard and MIT, Cambridge, 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NCCN Clinical Practice Guidelines in Oncology. Breast cancer. Version 3.2025. March 18, 2025. Accessed on March 20, 2025. https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1419"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2850882\/jamaoncology_tarantino_2026_br_260010_1787161707.8129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:02:42Z","timestamp":1787238162000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2850882"}},"subtitle":["A Secondary Analysis of the DAPHNe Trial"],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":11,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2026.2023","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}