{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:02:39Z","timestamp":1790751759956,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The optimal chemotherapy strategy after progression on cyclin\u2010dependent kinase 4\/6 inhibitors (CDK4\/6i) in hormone receptor\u2010positive\/human epidermal growth factor receptor 2\u2010negative (HR+\/HER2\u2212) metastatic breast cancer remains a matter of controversy. This study evaluated the efficacy of metronomic chemotherapy compared with other post\u2010CDK4\/6i treatment strategies in a real\u2010world setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>This retrospective multicenter study included patients with HR+\/HER2\u2212 metastatic breast cancer progressing on CDK4\/6i plus endocrine therapy and subsequently treated with systemic therapy. Progression\u2010free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety. Propensity score matching (1:2) was performed to reduce selection bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 177 patients were included, of whom 52 (29.4%) received metronomic chemotherapy. Among treatment strategies, metronomic chemotherapy achieved the longest median PFS (9\u2009months; 95% CI: 5.46\u201312.53;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). In multivariable analysis, metronomic chemotherapy was independently associated with prolonged PFS (HR 0.46, 95% CI: 0.30\u20130.69;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Median OS did not significantly differ across treatment groups. ORR was 48.0%, and CBR was 60.0% with metronomic chemotherapy. After propensity score matching, metronomic chemotherapy maintained a significant association with improved PFS (HR 0.49, 95% CI: 0.31\u20130.78;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Toxicities were predominantly Grade 1\u20132, with no severe adverse events reported in the metronomic cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this real\u2010world study, metronomic chemotherapy was associated with improved disease control and a favorable safety profile in patients with HR+\/HER2\u2212 metastatic breast cancer progressing after CDK4\/6i\u2010based therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Protocol Number 0037558\/23<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72325","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:39:08Z","timestamp":1790750348000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of Metronomic Chemotherapy in Hormone Receptor\u2010Positive\/\n                    <scp>HER2<\/scp>\n                    \u2010Negative Metastatic Breast Cancer: A Retrospective Multicenter Study"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-6251","authenticated-orcid":false,"given":"Lara","family":"Laini","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology University of Brescia, ASST Spedali Civili  Brescia Italy"},{"name":"Medical Oncology Istituto Clinico Sant'anna  Brescia 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