{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:06:45Z","timestamp":1790723205043,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":307,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Breast Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>HER2\u2010low status is a predictive factor for novel anti\u2010HER2 therapies in metastatic hormone receptor\u2013positive breast cancer (HR+ MBC). However, its impact on endocrine therapy outcomes remains uncertain. We aimed to explore the effect of HER2\u2010low and HER2\u2010zero status in HR+ MBC patients treated with first\u2010line aromatase inhibitors (AIs) with or without CDK4\/6 inhibitors (CDK4\/6i).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed postmenopausal women with HR+ MBC treated with first\u2010line AI\u2009\u00b1\u2009CDK4\/6i between January 1, 2017, and December 31, 2022, from six tertiary hospitals in Thailand. HER2\u2010low was defined as HER2 IHC 1+ or IHC 2+ with ISH\u2010negative. Progression\u2010free survival (PFS) and overall survival (OS) were compared in unadjusted and adjusted cohorts using stabilized inverse probability of treatment weighting (sIPTW), adjusting for age, ECOG performance status, de novo metastasis, endocrine sensitivity, visceral metastasis, number of metastatic sites, and treatment year. Interaction analyses were performed to assess effect modification by HER2 status and other clinical subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 504 patients, 219 (43.5%) were HER2\u2010low, and 285 (56.5%) were HER2\u2010zero. Median follow\u2010up was 31 months (IQR 19\u201347). CDK4\/6i\u2009+\u2009AI was administered to 52.5% of HER2\u2010low and 43.9% of HER2\u2010zero patients. After sIPTW adjustment, CDK4\/6i\u2009+\u2009AI prolonged median PFS to 22.1 months compared with 21.5 months for AI alone in the HER2\u2010low cohort (HR = 0.80, 95% CI 0.54\u20131.18;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.26) and to 20.1 months compared with 13.5 months in the HER2\u2010zero cohort (HR = 0.65, 95% CI 0.45\u20130.93;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.02). Median OS was 49.3 months with CDK4\/6i\u2009+\u2009AI versus 48.4 months with AI alone in HER2\u2010low (HR = 0.81, 95% CI 0.48\u20131.36;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.43) and 45.8 versus 42.3 months in HER2\u2010zero (HR = 0.85, 95% CI 0.43\u20131.05;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.52). Subgroup analyses showed consistent benefit of CDK4\/6i\u2009+\u2009AI across most clinical categories. The interaction test for treatment\u2009\u00d7\u2009HER2 status was not significant (HR = 1.21, 95% CI 0.74\u20131.98;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.44), indicating no effect modification by HER2\u2010low status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HER2\u2010low status was not associated with prognosis or predictive value for CDK4\/6i efficacy, supporting CDK4\/6i\u2009+\u2009AI as the standard first\u2010line therapy irrespective of HER2 expression level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijbc\/5597051","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:20:38Z","timestamp":1762323638000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Outcomes of HER2\u2010Low Versus HER2\u2010Zero in HR\u2010Positive Metastatic Breast Cancer Treated With Endocrine Therapy With or Without CDK4\/6 Inhibitors: A Multicenter Retrospective 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