{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:25:59Z","timestamp":1781191559949,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"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:p>\u201cPrimary neuroendocrine breast carcinoma (NEBC) is an underdiagnosed subtype of breast cancer, which includes small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Accurate diagnosis remains challenging given their low incidence; misclassification as invasive breast carcinoma of no special type (IBC-NST), invasive ductal carcinoma (IDC), or a metastatic neuroendocrine carcinoma may occur. Cases with any component of adenocarcinoma and well-differentiated neuroendocrine tumors were excluded. A search of the pathology database (2012\u20132024) revealed six female patients (27\u201385\u202fyears) with a final pathologic diagnosis of NEBC (stages IA\u2013IV), including four diagnosed with LCNEC and two with SCNEC. Even though most NEBC cases (5 of 6; 83%) were of the luminal subtype, five of six patients (83%) developed distant metastases within 4\u202fyears of the initial diagnosis. Molecular profiling of six cases revealed common alterations in the FGF\/FGFR and PI3K\/AKT\/mTOR pathways. In summary, primary neuroendocrine carcinomas of the breast display aggressive behavior. However, they are more likely to harbor certain alterations, such as activating <jats:italic>PIK3CA<\/jats:italic> mutations and <jats:italic>FGFR1<\/jats:italic> amplification, which can be of therapeutic value. The Ki-67 index, unlike in the pancreas and gastrointestinal tract, is not suitable for grading neuroendocrine neoplasms (NENs) of the breast. However, it can still serve as a tool for risk stratification, similar to its use in luminal-type breast cancer.<\/jats:p>","DOI":"10.3389\/fmed.2025.1551309","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:36:21Z","timestamp":1755668181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Neuroendocrine carcinoma of the breast: a review of the literature and illustration of six cases"],"prefix":"10.3389","volume":"12","author":[{"given":"Nazire E.","family":"Albayrak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1111\/his.12463","article-title":"Papillary and neuroendocrine breast lesions: the WHO stance","volume":"66","author":"Tan","year":"2015","journal-title":"Histopathology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/1471-2407-14-147","article-title":"Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database","volume":"14","author":"Wang","year":"2014","journal-title":"BMC Cancer"},{"key":"ref3","volume-title":"Pathology and genetics of tumours of the breast and female genital organs: WHO classification of Tumours series","author":"Tavassoli","year":"2003"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1046\/j.1365-2559.2002.01336.x","article-title":"Neuroendocrine differentiation and prognosis in breast adenocarcinoma","volume":"40","author":"Miremadi","year":"2002","journal-title":"Histopathology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"408459","DOI":"10.1155\/2014\/408459","article-title":"Expression of neuroendocrine markers in different molecular subtypes of breast carcinoma","volume":"2014","author":"Wachter","year":"2014","journal-title":"Biomed Res Int"},{"key":"ref6","volume-title":"WHO classification of Tumours of the breast","author":"Tan","year":"2019"},{"key":"ref7","year":""},{"key":"ref8","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","year":"2012","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"R219","DOI":"10.1530\/ERC-19-0483","article-title":"Extrapulmonary poorly differentiated NECs, including molecular and immune aspects","volume":"27","author":"McNamara","year":"2020","journal-title":"Endocr Relat Cancer"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"644434","DOI":"10.3389\/fonc.2021.644434","article-title":"Profiling of 520 candidate genes in 50 surgically treated Chinese small cell lung Cancer patients. 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