{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:06:41Z","timestamp":1790723201852,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Accumulating data demonstrate the robust overall and intracranial activity of trastuzumab deruxtecan (T\u2010DXd) in HER2\u2010positive breast cancer brain metastasis (BCBM). Limited data are available on HER2\u2010low\/zero BCBM, as well as patients with symptomatic active BM, leptomeningeal disease (LMD), and poor performance status. This multicenter, retrospective, real\u2010world study enrolled patients diagnosed with HER2\u2010positive or low\/zero BCBM receiving T\u2010DXd. Progression\u2010free survival (PFS), intracranial progression\u2010free survival (IC\u2010PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), IC\u2010ORR, IC\u2010DCR, and adverse events (AEs) were evaluated. From January 2020 to July 2024, 58 HER2\u2010positive and 30 HER2\u2010low\/zero patients were enrolled. In the HER2\u2010positive cohort, the median PFS, IC\u2010PFS, and OS were 11, 13, and 46\u2009months, respectively. ORR and DCR were 65.2% and 91.3% systemically, with IC\u2010ORR and IC\u2010DCR of 61.0%\/90.2% (RECIST 1.1) and 59.5%\/88.1% (RANO\u2010BM). In the HER2\u2010low\/zero cohort, median PFS, IC\u2010PFS, and OS were 4, 5, and 26\u2009months. ORR and DCR were 33.3% and 66.7%. IC\u2010ORR and IC\u2010DCR were 44.4% and 88.9% by RECIST 1.1 and RANO\u2010BM. HR+\/HER2\u2010low patients had significantly longer PFS than HR\u2010\/HER2\u2010low (10 vs. 3\u2009months,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In the LMD cohort, the 12\u2010month IC\u2010PFS rates were 67.7% and 60.0% in HER2\u2010positive and low\/zero cohorts. The most common AEs included fatigue (45.9%) and appetite loss (25.2%). Seven (8.0%) patients suffered interstitial lung disease (ILD), including 2 (2.3%) grade 3. T\u2010DXd showed substantial and durable overall and intracranial efficacy in HER2\u2010positive and low\/zero BCBM, including challenging subgroups with active BM or LMD.\n                  <\/jats:p>","DOI":"10.1111\/cas.70181","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T06:05:55Z","timestamp":1757657155000},"page":"3149-3159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of T\u2010\n                    <scp>DXd<\/scp>\n                    in\n                    <scp>HER2<\/scp>\n                    + and Low\/Zero Metastatic\n                    <scp>BCBM<\/scp>\n                    : A Retrospective Multicenter Real\u2010World Study"],"prefix":"10.1111","volume":"116","author":[{"given":"Qingru","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Nongken Central Hospital of Guangdong Province  Zhanjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"He","sequence":"additional","affiliation":[{"name":"Department of Radiology, Sun Yat\u2010Sen University Cancer Center State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guorong","family":"Zou","sequence":"additional","affiliation":[{"name":"Central Hospital of pan\u2010Yu  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqian","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3425-2324","authenticated-orcid":false,"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Dun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejun","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongguan People's Hospital  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yabing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Oncology Kiang Wu Hospital  Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5414-8049","authenticated-orcid":false,"given":"Yanxia","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Sun Yat\u2010Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-503X","authenticated-orcid":false,"given":"Yonggao","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Department State Key Laboratory of Oncology in South China Sun Yat\u2010Sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-7285","authenticated-orcid":false,"given":"Anli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department 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