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While most studies focus on primary tumors, there is limited data on metastatic disease. Here, we aimed to evaluate the clinicopathological features, metastatic patterns and biomarker discordance in HER2-low\/UL metastatic breast cancers. The HER2 status in a large cohort of metastatic breast cancer cases was correlated with different pathological and survival parameters. Data from matched primary tumours were also retrieved for further comparisons. HER2-low metastatic breast cancer is significantly associated with ER positivity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033), PR positivity (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.037) and Luminal status (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.047), but no distinct overall survival. These tumors were preferentially found in liver metastases (42.9%), differing significantly from HER2-zero cancers (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Downregulation of HER2-positive primaries to HER2-negative metastasis was found to be the highest in liver (50.0%), and the least in lung (0%). Downregulation of HER2 is associated with poorer OS (Chi-sq\u2009=\u20099.248,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002). In metastatic settings, features and survival outcomes of HER2-UL are not significantly distinct from HER2-null tumors. HER2-low metastatic cancers largely retain clinicopathological characteristics of their primary origins. Liver is the predominant site of HER2-low metastasis and shows a notable risk of HER2 discordance. Given that discordance, particularly the link of worse outcome to HER2 downregulation, re-evaluation of biomarker status in high-risk sites should be considered to optimise therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1007\/s00428-026-04710-z","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:33:16Z","timestamp":1789198396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HER2-low metastatic breast cancers: clinic-pathological characteristics, metastatic sites, and survival impact on biomarker discordance"],"prefix":"10.1007","author":[{"given":"Ka Long","family":"Leung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaiwat","family":"Aphivatanasiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Bi","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Y","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Chi Eric","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajiang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-9665","authenticated-orcid":false,"given":"Gary M","family":"Tse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"issue":"1","key":"4710_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2203690","volume":"387","author":"S Modi","year":"2022","unstructured":"Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E et al (2022) Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. 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