{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:46:51Z","timestamp":1785732411405,"version":"3.56.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"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. Oncol."],"abstract":"<jats:p>Antibody-drug conjugates (ADCs) have shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and brain metastases. This study aimed to investigate the efficacy and safety of brain radiotherapy combined with ADCs in patients with HER2-positive breast cancer and brain metastases in routine Chinese clinical practice. We retrospectively analyzed data from 35 patients with HER2-positive breast cancer and brain metastases treated with brain radiotherapy plus trastuzumab deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1) at the Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, between January 2023 and January 2025. Most patients had prior pyrotinib treatment. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), and treatment safety were analyzed. Median follow-up was 15.7 months (interquartile range [IQR], 8.7\u201320.8). Median iPFS was 8.4 months (95% confidence interval [CI] 6.9\u20139.8), median PFS was 7.9 months (95% CI 5.9\u201310.4), and median OS was 11.8 months (95% CI 8.6\u201313.8). Intracranial objective response rate (ORR) was 74.3%, and intracranial disease control rate (DCR) was 94.3%. Median iPFS was 7.6 months in the T-DM1 group versus 10.9 months in the T-DXd group (P &amp;lt; 0.001); median PFS was 6.5 months versus 9.7 months (P\u00a0=\u00a00.021); median OS was 10.4 months versus 12.9 months (P\u00a0=\u00a00.046). The most common grade \u22653 adverse events were decreased appetite (23%), fatigue (11%), leukopenia (11%), and thrombocytopenia (9%). Among adverse events of special interest, radiation necrosis occurred in 9% (3\/35), all were grade 1\u20132 and occurred exclusively in patients receiving concurrent radiotherapy plus T-DM1; interstitial lung disease occurred in 3% (1\/35), grade 1, in the T-DXd group. In Chinese clinical practice, brain radiotherapy combined with either T-DXd or T-DM1 showed promising preliminary efficacy and tolerable safety signals in heavily pyrotinib-pretreated HER2-positive breast cancer patients with brain metastases in this retrospective single-center cohort. In this unadjusted retrospective cohort, patients receiving radiotherapy combined with T-DXd exhibited longer univariate survival outcomes compared with those treated with T-DM1. However, these univariate observational results are preliminary and require prospective multicenter validation with multivariate adjustment.<\/jats:p>","DOI":"10.3389\/fonc.2026.1899301","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:28:10Z","timestamp":1785731290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of brain radiotherapy combined with antibody-drug conjugates in patients with HER2-positive breast cancer brain metastases"],"prefix":"10.3389","volume":"16","author":[{"given":"Dongxing","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyou","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, 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