{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:15:47Z","timestamp":1788437747446,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"9","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":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Background\/Objectives: Neoadjuvant therapy (NAT) may remodel the breast-cancer microenvironment. We evaluated paired changes in programmed death-ligand 1 (PD-L1), vascular endothelial growth factor (VEGF), and tumor-infiltrating lymphocytes (TILs) before and after NAT, and associations with the residual cancer burden (RCB) and survival. Methods: This retrospective study included 102 patients with residual invasive breast cancer after NAT: 34 with luminal B-like\/HER2-negative, 34 with luminal B-like\/HER2-positive, and 34 with triple-negative breast cancer (TNBC). PD-L1 was assessed using the 22C3 combined positive score, VEGF by the cytoplasmic staining intensity, and stromal TILs according to international recommendations. Results: The median tumor size decreased from 2.5 to 1.7 cm (p &lt; 0.001), the PD-L1 CPS (combined positive score) from 6 to 5 (p = 0.039), and the TILs from 15% to 10% (p &lt; 0.001), whereas VEGF shifted toward stronger staining (p = 0.03). In TNBC, the PD-L1 CPS decreased from 10 to 5 (p = 0.003) and the TILs from 20% to 8% (p &lt; 0.001). Biomarkers were not associated with the RCB in the overall cohort. The initial tumor size predicted RCB II\/III (OR: 2.60, p = 0.038). The overall survival differed by subtype (p &lt; 0.001). Conclusions: NAT has induced subtype-dependent immune and angiogenic changes, supporting biomarker reassessment in residual disease.<\/jats:p>","DOI":"10.3390\/cimb48090899","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:53Z","timestamp":1788433733000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Changes in PD-L1, VEGF, and TILs Following Neoadjuvant Therapy in Residual Invasive Breast Cancer"],"prefix":"10.3390","volume":"48","author":[{"given":"Marina","family":"Bakula","sequence":"first","affiliation":[{"name":"Clinical Institute of Pathology and Forensic Medicine, University Hospital Center Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jasmina","family":"Rajc","sequence":"additional","affiliation":[{"name":"Clinical Institute of Pathology and Forensic Medicine, University Hospital Center Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Ana","family":"Kvolik Pavic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Maxillofacial and Oral Surgery, University Hospital Center Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-9585","authenticated-orcid":false,"given":"Slavica","family":"Kvolik","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"},{"name":"Department of Anesthesiology, Intensive Care Medicine and Pain Management, University Hospital Center Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/S0140-6736(20)32381-3","article-title":"Breast cancer","volume":"397","author":"Loibl","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","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. 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