{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:20Z","timestamp":1783574120101,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["\u4e0dSZSM202211036"],"award-info":[{"award-number":["\u4e0dSZSM202211036"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503188"],"award-info":[{"award-number":["82503188"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["KCXFZ20200201101050887, ZDSYS20190902092855097"],"award-info":[{"award-number":["KCXFZ20200201101050887, ZDSYS20190902092855097"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Primary breast squamous cell carcinoma (PBSCC) with HER2-positive status is exceptionally rare, with fewer than 100 cases reported globally, and HER2 positivity occurring in only 5.8-7.1% of these cases. No established treatment standards exist for this entity. We present the case of a 43-year-old woman with HER2-positive PBSCC who exhibited a poor response to neoadjuvant TCHP therapy (Miller-Payne grade 2). Local recurrence occurred just 3 months after mastectomy. Second-line therapy with pyrotinib plus capecitabine provided 9 months of disease control before lung metastasis emerged. Subsequent molecular profiling revealed a\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    E545K mutation (VAF 40.3%), co-amplified with\n                    <jats:italic>FGF3\/4\/19<\/jats:italic>\n                    and\n                    <jats:italic>CCND1<\/jats:italic>\n                    . Although third-line treatment with trastuzumab deruxtecan (T-DXd) achieved a partial response, the progression-free survival (PFS) was limited to only 5 months. A repeat biopsy confirmed HER2 downregulation (from 3+ to 2+), identifying antigen loss as a key mechanism of acquired resistance. A review of the literature indicates that the pathological complete response rate of HER2-positive PBSCC to standard HER2-targeted therapy is remarkably low, far inferior to the 50-60% pCR rates achieved with dual HER2 blockade in HER2-positive invasive ductal carcinoma. This case underscores that upon failure of HER2-targeted therapy accompanied by HER2 antigen loss, the treatment strategy should pivot towards molecularly-guided precision therapy. Based on evidence such as that from the TRIUMPH trial, priority should be given to agents targeting the detected alterations, such as\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    or\n                    <jats:italic>FGFR<\/jats:italic>\n                    inhibitors, rather than persisting with HER2-targeted approaches.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1781401","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:29Z","timestamp":1783571009000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical features and treatment challenges of HER2-positive primary breast squamous cell carcinoma: a case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Fang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Oncology, Peking University Shenzhen 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