{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:13:31Z","timestamp":1788416011506,"version":"build-2803163510"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oral selective estrogen receptor degraders (SERDs) have become a key therapeutic option for hormone receptor-positive, HER2\u2212negative advanced breast cancer. The recent presentation of lidERA\u2014the first positive adjuvant Phase III trial of any oral SERD\u2014necessitates a comprehensive evidence synthesis spanning both early and advanced disease settings, beyond the scope of existing meta-analyses confined to metastatic disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review was prospectively registered (PROSPERO CRD420261358420). We searched PubMed, Cochrane CENTRAL, and conference abstract archives (SABCS, ESMO, ASCO; 2020\u20132026) for Phase II\/III randomized controlled trials comparing oral SERDs (giredestrant, imlunestrant, elacestrant, camizestrant, vepdegestrant, amcenestrant) with standard endocrine therapy in ER-positive, HER2\u2212negative breast cancer. Progression-free survival hazard ratios in the metastatic setting were pooled using random-effects models. Prespecified sensitivity analyses included Bayesian re-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ten randomized controlled trials met inclusion criteria (one adjuvant, n = 4,170; nine metastatic). Giredestrant significantly improved invasive disease-free survival in the adjuvant lidERA trial (HR 0.70; 95% CI 0.57\u20130.87;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0014). In the metastatic setting, pooled analysis of six oral degrader monotherapy trials (n = 2,502) showed a progression-free survival benefit (HR 0.815; 95% CI 0.718\u20130.924;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0014) with moderate heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      \u00b2 = 35.2%). The\n                      <jats:italic>ESR1<\/jats:italic>\n                      -mutated subgroup revealed a particularly robust and consistent effect (HR 0.617; 95% CI 0.527\u20130.723;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.0001) with zero heterogeneity across five independent trials (\n                      <jats:italic>I<\/jats:italic>\n                      \u00b2 = 0%). These findings were unchanged across all sensitivity analyses: restriction to Phase III trials only (HR 0.811;\n                      <jats:italic>I<\/jats:italic>\n                      \u00b2 = 5.8%), exclusion of the PROTAC agent (HR 0.807), leave-one-out iteration (range 0.790\u20130.843), and Bayesian re-analysis (posterior median HR 0.814; 95% credible interval 0.678\u20130.969). Egger\u2019s test did not detect significant funnel plot asymmetry (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.40), though power was limited (k = 6).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Oral SERDs confer a consistent progression-free survival benefit in advanced breast cancer, with the most robust and consistent effect in\n                      <jats:italic>ESR1<\/jats:italic>\n                      -mutated tumors. Giredestrant is the first oral SERD to achieve significantly improved invasive disease-free survival in the adjuvant setting, marking a potential new standard of care. This evidence synthesis across the full breast cancer continuum offers a framework for clinical decision-making as oral SERDs expand from advanced to early-stage disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php<\/jats:ext-link>\n                      , identifier CRD420261358420.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1896847","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:44Z","timestamp":1788412964000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral selective estrogen receptor degraders in ER+\/HER2\u2212 breast cancer: a systematic review with pooled analysis of metastatic randomized trials and narrative synthesis of adjuvant evidence"],"prefix":"10.3389","volume":"16","author":[{"given":"Bing","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Pathology, Suzhou BenQ Medical Center","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Suzhou BenQ Medical Center","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Suzhou BenQ Medical Center","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Suzhou BenQ Medical Center","place":["Suzhou, 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