{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:17:54Z","timestamp":1791908274996,"version":"4.3.4"},"reference-count":120,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and clinical relevance. PNI is most frequently observed in high-grade invasive ductal carcinoma (IDC), particularly in triple-negative and HER2-positive subtypes. It is also seen in special histological subtypes such as mixed, metaplastic, and invasive micropapillary carcinomas. Mechanistically, PNI involves tumor\u2013neural interactions, including neurotrophic factor signaling and epithelial\u2013mesenchymal transition, contributing to tumor progression and potential locoregional recurrence (LRR). While PNI is linked to adverse prognosis in other tumors, its independent role remains unclear in breast cancer due to limited large-scale studies. Therefore, further investigation into its prognostic significance and potential therapeutic implications is needed. Future research should focus on refining diagnostic criteria and assessing targeted therapies to mitigate PNI-associated progression. This review summarizes the current knowledge on perineural invasion (PNI) in breast cancer, addressing its histological features, molecular mechanisms, diagnostic challenges, and clinical implications.<\/jats:p>","DOI":"10.3390\/cancers17121900","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:43:14Z","timestamp":1749202994000},"page":"1900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Perineural Invasion in Breast Cancer: A Comprehensive Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-2595","authenticated-orcid":false,"given":"Hisham F.","family":"Bahmad","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4637-6423","authenticated-orcid":false,"given":"Carter","family":"Wegner","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Nuraj","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Avellan","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3327-1988","authenticated-orcid":false,"given":"Jeffrey","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresita","family":"Mendez","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Jabbour","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Lebanese University, Hadath Campus, Beirut 1003, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-2428","authenticated-orcid":false,"given":"Carmen","family":"Gomez-Fernandez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1002\/cncr.24396","article-title":"Perineural invasion in cancer","volume":"115","author":"Liebig","year":"2009","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1177\/1066896907302236","article-title":"Perineural and Intraneural \u201cInvasion\u201d in Benign Proliferative Breast Disease","volume":"15","author":"Fellegara","year":"2007","journal-title":"Int. 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