{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:17:22Z","timestamp":1792275442755,"version":"4.4.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analyses<\/jats:title><jats:p>This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148\/21, version 3, 1\/2\/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p><jats:uri>ClinicalTrials.gov<\/jats:uri>, identifier number NCT04889924.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1184021","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T17:26:50Z","timestamp":1691602010000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)"],"prefix":"10.3389","volume":"13","author":[{"given":"Amparo","family":"Garcia-Tejedor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ortega-Exposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sira","family":"Salinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Luzardo-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Falo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Martinez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"P\u00e9rez-Montero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Teresa","family":"Soler-Mons\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Teresa","family":"Bajen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Benitez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Guma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Pl\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Pernas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Pe\u00f1afiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Yeste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gil-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Guedea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Ponce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Laplana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2016.07.018","article-title":"Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? an updated meta-analysis involving 3,398 patients","volume":"212","author":"El Hage Chehade","year":"2016","journal-title":"Am J Surg"},{"key":"B2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3233\/BD-210043","article-title":"Risk factors for lymphedema after breast surgery: a prospective cohort study in the era of sentinel lymph node biopsy","volume":"41","author":"Salinas-Huertas","year":"2022","journal-title":"Breast Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.11470","article-title":"Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial","volume":"318","author":"Giuliano","year":"2017","journal-title":"JAMA - J Am Med Assoc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70460-7","article-title":"AMAROS trial","volume":"15","author":"Donker","year":"2015","journal-title":"Lancet Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S1470-2045(13)70035-4","article-title":"Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial","volume":"14","author":"Galimberti","year":"2013","journal-title":"Lancet Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ijsu.2016.08.022","article-title":"Recommendation for axillary lymph node dissection in women with early breast cancer and sentinel node metastasis: a systematic review and meta-analysis of randomized controlled trials using the GRADE system","volume":"34","author":"Huang","year":"2016","journal-title":"Int J Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/srep26304","article-title":"Axillary radiotherapy: an alternative treatment option for adjuvant axillary management of breast cancer","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0452-2","article-title":"The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors","volume":"16","author":"Tsai","year":"2009","journal-title":"Ann Surg Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/SAP.0000000000001864","article-title":"Lymphedema incidence after axillary lymph node dissection: quantifying the impact of radiation and the lymphatic microsurgical preventive healing approach","volume":"82","author":"Johnson","year":"2019","journal-title":"Ann Plast Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25152","article-title":"Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer","volume":"116","author":"Dominici","year":"2010","journal-title":"Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5246-8","article-title":"How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? results of a prospective study","volume":"23","author":"Mamtani","year":"2016","journal-title":"Ann Surg Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05970-2","article-title":"Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC","volume":"185","author":"Garcia-Tejedor","year":"2021","journal-title":"Breast Cancer Res Treat"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70160-3","article-title":"Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial","volume":"15","author":"Von Minckwitz","year":"2014","journal-title":"Lancet Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"103223","DOI":"10.1016\/j.critrevonc.2021.103223","article-title":"Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: a systematic review and meta-analysis of randomized clinical trials","volume":"159","author":"Tarantino","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00069","article-title":"Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update","volume":"34","author":"Andre","year":"2022","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.07.2460","article-title":"Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer: In vitro sonographic study","volume":"191","author":"Bedi","year":"2008","journal-title":"Am J Roentgenol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1148\/rg.335125214","article-title":"Response criteria in oncologic imaging: review of traditional and new criteria","volume":"33","author":"Tirkes","year":"2013","journal-title":"Radiographics"},{"key":"B18","article-title":"The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the international society of lymphology","volume":"49","year":"2016","journal-title":"Lymphology"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1184021\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T17:26:52Z","timestamp":1691602012000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1184021\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":18,"alternative-id":["10.3389\/fonc.2023.1184021"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1184021","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]},"article-number":"1184021"}}