{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T09:01:59Z","timestamp":1784710919930,"version":"3.55.0"},"reference-count":44,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Shanghai YRD Foundation for Innovation in Health Industry","award":["2025-YRDFHI-060"],"award-info":[{"award-number":["2025-YRDFHI-060"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The optimal systemic treatment for node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer with tumors &gt;2\u2009cm remains unclear. De-escalation is commonly used for smaller tumors, but evidence supporting the neoadjuvant dual-targeted pathway in high tumor burden disease is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To compare pathological response and exploratory disease-free survival (DFS) between the neoadjuvant dual-targeted and adjuvant single-targeted treatment pathways, focusing on tumors &gt;2\u2009cm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Retrospective, single-center cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We identified 518 consecutive patients treated from 2015 to 2023 at a tertiary academic center. In a guideline-recommended cohort (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2009=\u2009426), patients managed via the neoadjuvant dual-targeted pathway were compared with those managed via the adjuvant single-targeted pathway. Propensity scores were estimated using logistic regression and applied via overlap weighting to balance covariates. DFS was assessed using overlap-weighted Cox regression, including a tumor-size interaction (\u2a7d2 vs &gt;2\u2009cm). Sensitivity analyses addressed calendar-time confounding, truncation at 24\u2009months with bootstrapped risk differences, and surgery-date landmark analysis. Reporting followed Strengthening the Reporting of Observational Studies in Epidemiology guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Overlap weighting achieved good balance (all standardized mean differences &lt;0.10). In the guideline-recommended cohort (18 DFS events), the neoadjuvant dual-targeted pathway was not significantly associated with DFS (hazard ratio (HR) 0.26; 95% confidence interval (CI): 0.04\u20131.55;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.138), and the size-by-treatment interaction was not significant (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.123). In tumors &gt;2\u2009cm (\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      \u2009=\u2009247), the neoadjuvant dual-targeted pathway was associated with a pathological complete response rate of 56.9% (58\/102) and an exploratory DFS signal (HR 0.08; 95% CI: 0.01\u20130.59). At 24\u2009months, 0 versus 5 DFS events resulted in an absolute risk difference of 7.0% (95% CI: 1.1%\u201314.0%). Sensitivity analyses yielded consistent results, though estimates for tumors \u2a7d2\u2009cm were imprecise.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In this exploratory real-world cohort, the neoadjuvant dual-targeted treatment pathway for node-negative, HER2-positive breast cancer with tumors &gt;2\u2009cm was associated with high pathological response rates and an exploratory DFS signal, though sparse events and observational biases limit survival conclusions. Size-informed, risk-adapted strategies are needed.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">Trial registration<\/jats:italic>\n                        :\n                      <\/jats:bold>\n                      Not applicable.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261465352","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:10:48Z","timestamp":1784527848000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumors &gt;2\u2009cm in node-negative, HER2-positive breast cancer: comparing neoadjuvant dual-targeted versus adjuvant single-targeted treatment pathways in real-world practice"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1418-5760","authenticated-orcid":false,"given":"Xiaoduo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The First 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