{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:32:39Z","timestamp":1793226759828,"version":"4.5.0"},"reference-count":51,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"31","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Over the past three decades, the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has undergone a remarkable transformation. Once associated with poor outcomes and a median survival of &lt;2 years in the metastatic setting, HER2-positive metastatic breast cancer is at present increasingly managed for years, with long-term survival beyond 5 years becoming common. Parallel advances in early-stage therapy have substantially reduced recurrence rates and altered the clinical landscape of metastatic disease, with a growing proportion of patients currently presenting with de novo metastatic disease rather than relapse after prior HER2-directed treatment. These improvements have been driven by successive generations of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates. Most recently, trastuzumab deruxtecan (T-DXd) has demonstrated unprecedented efficacy and is rapidly moving earlier in treatment algorithms across both metastatic and curative-intent settings. This shift raises important questions regarding optimal sequencing, toxicity management\u2014particularly for interstitial lung disease\u2014and the downstream implications for other HER2-directed therapies. In this review, we summarize the evolution of HER2-targeted therapy and discuss strategies for managing HER2-positive breast cancer across disease stages in the era of earlier treatment with T-DXd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-26-00672","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:59:32Z","timestamp":1783972772000},"page":"3061-3069","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Current Management of Human Epidermal Growth Factor Receptor 2\u2013Positive Breast Cancer in a Changing Landscape"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-6383","authenticated-orcid":false,"given":"Marla","family":"Lipsyc-Sharf","sequence":"first","affiliation":[{"name":"University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-7191","authenticated-orcid":false,"given":"Sara A.","family":"Hurvitz","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2470152"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103153441101"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa064320"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.6725"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70130-X"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113216"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30863-0"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209124"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.4887"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914510"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02420-5"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03021-7"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2508668"},{"key":"e_1_3_5_15_2","volume-title":"PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer (DEMETHER)","year":"2025","unstructured":"PHESGO Maintenance After T-DXd Short Induction for HER2+ Unresectable Locally Recurrent or Metastatic Breast Cancer (DEMETHER). 2025. https:\/\/clinicaltrials.gov\/study\/NCT06172127"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2511218"},{"key":"e_1_3_5_17_2","article-title":"HER2CLIMB-05: A phase III study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer","author":"Dieras V","unstructured":"Dieras V, Curigliano G, Martin M, et al: HER2CLIMB-05: A phase III study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. 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