{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:13:31Z","timestamp":1788416011453,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neoadjuvant systemic therapy (NST) has become a cornerstone in the management of aggressive early breast cancer (BC) subtypes, including triple-negative (eTNBC) and HER2-positive disease. Immune checkpoint inhibition with pembrolizumab represents an active immunotherapeutic approach, whereas dual HER2 blockade with trastuzumab and pertuzumab constitutes passive immunotherapy in early HER2-positive BC. Although both strategies demonstrate substantial antitumor efficacy, real-world data directly comparing their surgical safety profiles are limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This retrospective single-center cohort study included 99 patients with early BC treated with NST between 2014 and 2025. A total of 33 patients with TNBC received pembrolizumab-based therapy according to the KEYNOTE-522 regimen, whereas 66 patients with HER2-positive disease received chemotherapy combined with trastuzumab and pertuzumab. Surgical adverse events within 30 days postoperatively were assessed using the Clavien\u2013Dindo classification and the Comprehensive Complication Index (CCI). Complication rates and severity were compared between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overall postoperative complication rate was 25.3%, with no significant difference between TNBC and HER2-positive cohorts (27.3% vs. 24.2%,\n                      <jats:italic>p =<\/jats:italic>\n                      0.744). Most complications were minor (Clavien\u2013Dindo \u2264II), and rates of major complications (\u2265IIIa) did not differ between groups (\n                      <jats:italic>p =<\/jats:italic>\n                      0.706). Mean CCI scores were comparable (22.1 vs. 24.4;\n                      <jats:italic>p =<\/jats:italic>\n                      0.630). Seroma formation was the most frequent adverse event in both cohorts. In an exploratory multivariable logistic regression analysis, treatment group was not independently associated with postoperative complications. Pathological complete response rates were 63.6% in TNBC and 45.5% in HER2-positive patients. No clinically relevant delays in adjuvant radiotherapy occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>No statistically significant differences in postoperative morbidity were observed between treatment groups. These findings support the feasibility of integrating both neoadjuvant treatment strategies into routine surgical practice; however, confirmation in larger prospective studies is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1917346","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:40Z","timestamp":1788412960000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant pembrolizumab-based therapy versus dual HER2 blockade in early breast cancer: comparable surgical complication rates in a real-world cohort"],"prefix":"10.3389","volume":"13","author":[{"given":"Kerstin","family":"Wimmer","sequence":"first","affiliation":[{"name":"Department of General Surgery, Division of Visceral Surgery and Comprehensive Cancer Center, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Kantner","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Visceral Surgery and Comprehensive Cancer Center, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Exner","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Visceral Surgery and Comprehensive Cancer Center, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Bago-Horvath","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Oncology, Breast Health Center and Comprehensive Cancer Center, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Konrad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Fitzal","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Hanusch Hospital","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Marhold","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Division of Oncology, Medical University Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 Cancers in 185 Countries.","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin."},{"key":"B2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.annonc.2023.11.016","article-title":"Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up.","volume":"35","author":"Loibl","year":"2024","journal-title":"Ann Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/S1470-2045(16)00163-7","article-title":"5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial.","volume":"17","author":"Gianni","year":"2016","journal-title":"Lancet Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1056\/NEJMoa1703643","article-title":"Adjuvant pertuzumab and trastuzumab in early HER2-Positive breast cancer.","volume":"377","author":"von Minckwitz","year":"2017","journal-title":"N Engl J Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1200\/JCO.20.01204","article-title":"Adjuvant pertuzumab and trastuzumab in early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years\u2019 Follow-Up.","volume":"39","author":"Piccart","year":"2021","journal-title":"J Clin Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/S1470-2045(19)30863-0","article-title":"Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study.","volume":"21","author":"Swain","year":"2020","journal-title":"Lancet Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1056\/NEJMoa1910549","article-title":"Pembrolizumab for early triple-negative breast cancer.","volume":"382","author":"Schmid","year":"2020","journal-title":"N Engl J Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.annonc.2024.02.002","article-title":"Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522.","volume":"35","author":"Pusztai","year":"2024","journal-title":"Ann Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1056\/NEJMoa2409932","article-title":"Overall survival with pembrolizumab in early-stage triple-negative breast cancer.","volume":"391","author":"Schmid","year":"2024","journal-title":"N Engl J Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1097983","DOI":"10.3389\/fonc.2023.1097983","article-title":"Immunotherapy for HER-2 positive breast cancer.","volume":"13","author":"Yang","year":"2023","journal-title":"Front Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1093\/annonc\/mdt133","article-title":"Active immunotherapy in HER2 overexpressing breast cancer: current status and future perspectives.","volume":"24","author":"Milani","year":"2013","journal-title":"Ann Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s00005-019-00566-1","article-title":"HER2-Positive breast cancer immunotherapy: a focus on vaccine development.","volume":"68","author":"Arab","year":"2020","journal-title":"Arch Immunol Ther Exp."},{"key":"B13","doi-asserted-by":"publisher","first-page":"100361","DOI":"10.1016\/j.esmoop.2021.100361","article-title":"Vaccination against Her-2\/neu, with focus on peptide-based vaccines.","volume":"7","author":"Tobias","year":"2022","journal-title":"ESMO Open."},{"key":"B14","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev.immunol.19.1.275","article-title":"IgG FC receptors.","volume":"19","author":"Ravetch","year":"2001","journal-title":"Annu Rev Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1056\/NEJMra043186","article-title":"Trastuzumab\u2013mechanism of action and use in clinical practice.","volume":"357","author":"Hudis","year":"2007","journal-title":"N Engl J Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1080\/21645515.2016.1199310","article-title":"Pembrolizumab (Keytruda).","volume":"12","author":"Kwok","year":"2016","journal-title":"Hum Vaccin Immunother."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1056\/NEJMoa052306","article-title":"Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.","volume":"353","author":"Piccart-Gebhart","year":"2005","journal-title":"N Engl J Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.2174\/1381612820666140604145037","article-title":"Anti-HER2 cancer therapy and cardiotoxicity.","volume":"20","author":"Babar","year":"2014","journal-title":"Curr Pharm Des."},{"key":"B19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10549-021-06280-x","article-title":"Trastuzumab-induced cardiotoxicity: a review of clinical risk factors, pharmacologic prevention, and cardiotoxicity of other HER2-directed therapies.","volume":"188","author":"Dempsey","year":"2021","journal-title":"Breast Cancer Res Treat."},{"key":"B20","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/cpt.394","article-title":"Immune-Related adverse events from immune checkpoint inhibitors.","volume":"100","author":"Marrone","year":"2016","journal-title":"Clin Pharmacol Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fphar.2017.00049","article-title":"Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy.","volume":"8","author":"Kumar","year":"2017","journal-title":"Front Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1245\/s10434-024-16390-7","article-title":"Real-World outcomes with the KEYNOTE-522 regimen in early-stage triple-negative breast cancer.","volume":"32","author":"Connors","year":"2025","journal-title":"Ann Surg Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1016\/j.amjsurg.2020.06.053","article-title":"Evaluation of breast surgical oncology complications after single agent versus dual agent HER2 targeted neoadjuvant chemotherapy.","volume":"220","author":"Cullom","year":"2020","journal-title":"Am J Surg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"5180","DOI":"10.1245\/s10434-024-15359-w","article-title":"Impact of neoadjuvant chemoimmunotherapy on surgical outcomes and time to radiation in triple-negative breast cancer.","volume":"31","author":"Myers","year":"2024","journal-title":"Ann Surg Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s12672-024-01349-7","article-title":"Surgical outcomes following neoadjuvant chemotherapy with and without immunotherapy in patients with triple-negative breast cancer.","volume":"15","author":"Holt","year":"2024","journal-title":"Discov Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2275846","DOI":"10.1080\/2162402X.2023.2275846","article-title":"Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer.","volume":"12","author":"Marhold","year":"2023","journal-title":"Oncoimmunology."},{"key":"B27","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1097\/SLA.0000000000001804","article-title":"Surgical outcomes for mastectomy patients receiving neoadjuvant chemotherapy: a propensity-matched analysis.","volume":"265","author":"Bowen","year":"2017","journal-title":"Ann Surg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1001\/archsurg.2010.163","article-title":"Impact of chemotherapy on postoperative complications after mastectomy and immediate breast reconstruction.","volume":"145","author":"Warren Peled","year":"2010","journal-title":"Arch Surg."},{"key":"B29","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s12282-024-01570-w","article-title":"Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy.","volume":"31","author":"Nogi","year":"2024","journal-title":"Breast Cancer."},{"key":"B30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.breast.2020.11.023","article-title":"A systematic review and meta-analysis on the effect of neoadjuvant chemotherapy on complications following immediate breast reconstruction.","volume":"55","author":"Varghese","year":"2021","journal-title":"Breast."},{"key":"B31","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.suc.2022.11.003","article-title":"Cognitive bias and dissonance in surgical practice: a narrative review.","volume":"103","author":"Richburg","year":"2023","journal-title":"Surg Clin North Am."},{"key":"B32","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","article-title":"Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.","volume":"240","author":"Dindo","year":"2004","journal-title":"Ann Surg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/SLA.0b013e318296c732","article-title":"The comprehensive complication index: a novel continuous scale to measure surgical morbidity.","volume":"258","author":"Slankamenac","year":"2013","journal-title":"Ann Surg."},{"key":"B34","doi-asserted-by":"publisher","first-page":"110511","DOI":"10.1016\/j.ejso.2025.110511","article-title":"Impact of neoadjuvant immunotherapy on postoperative complications in oncoplastic breast cancer surgery.","volume":"51","author":"Barjot","year":"2025","journal-title":"Eur J Surg Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"110011","DOI":"10.1016\/j.ejso.2025.110011","article-title":"Real-world evidence of the efficacy of neoadjuvant pembrolizumab in triple-negative breast cancer: a surgeon\u2019s point of view.","volume":"51","author":"Park","year":"2025","journal-title":"Eur J Surg Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"5550","DOI":"10.1245\/s10434-026-19121-2","article-title":"Surgical outcomes after neoadjuvant pembrolizumab plus chemotherapy for triple-negative breast cancer: results from the randomized, placebo-controlled phase 3 KEYNOTE-522 study.","volume":"33","author":"Kuemmel","year":"2026","journal-title":"Ann Surg Oncol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"3933","DOI":"10.3390\/cancers17243933","article-title":"Adding neoadjuvant immunotherapy to chemotherapy in non-metastatic triple-negative breast cancer: a propensity-matched cohort study from a tertiary cancer center.","volume":"17","author":"Al-Masri","year":"2025","journal-title":"Cancers."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1001\/jama.2013.278932","article-title":"Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.","volume":"310","author":"Boughey","year":"2013","journal-title":"JAMA."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.1093\/annonc\/mdt182","article-title":"Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).","volume":"24","author":"Schneeweiss","year":"2013","journal-title":"Ann Oncol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1470-2045(11)70336-9","article-title":"Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial.","volume":"13","author":"Gianni","year":"2012","journal-title":"Lancet Oncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/S1470-2045(18)30570-9","article-title":"Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial.","volume":"19","author":"van Ramshorst","year":"2018","journal-title":"Lancet Oncol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/1750743X.2026.2662201","article-title":"Immune-related adverse events as predictors of pathological complete response in early-stage triple-negative breast cancer treated with pembrolizumab.","volume":"18","author":"G\u00fcren","year":"2026","journal-title":"Immunotherapy."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3554","DOI":"10.3390\/cancers17213554","article-title":"Impact of chemotherapy dose intensity on pathological complete response in pembrolizumab-treated early triple-negative breast cancer: a real-world multicenter analysis.","volume":"17","author":"Fedele","year":"2025","journal-title":"Cancers."},{"key":"B44","doi-asserted-by":"publisher","first-page":"116102","DOI":"10.1016\/j.ejca.2025.116102","article-title":"Association of neoadjuvant chemotherapy dose intensity with pathological complete response and event-free survival in HER2-negative early breast cancer.","volume":"232","author":"Buonaiuto","year":"2026","journal-title":"Eur J Cancer."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1917346\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:41Z","timestamp":1788412961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1917346\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":44,"alternative-id":["10.3389\/fmed.2026.1917346"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1917346","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1917346"}}