{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T09:48:21Z","timestamp":1782467301035,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Several novel oral estrogen receptor (ER) degraders have been shown to modestly improve progression-free survival (PFS) compared to standard endocrine therapy (ET) in patients carrying ESR1 mutations. However, whether overall survival (OS) is also improved is unknown. Methods: All randomized controlled trials (RCTs) comparing ER degraders to standard ET in patients with ER+HER2-metastatic breast cancer were identified. The efficacy outcomes included PFS and OS for the intention-to-treat (ITT) population and were stratified according to ESR1 status (mutated versus wildtype). Hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS were extracted and pooled into a meta-analysis. Results: Eight RCTs comprising 4230 patients were analyzed. Compared to standard ET, ER degraders were associated with statistically significant improvement in OS in the ITT population, with HR 0.81, 95% CI 0.69\u20130.95, p = 0.01. Analysis by ESR1 status demonstrated that ER degraders were associated with significant improvement in the OSs for patients with an ESR1 mutation (HR = 0.70, 95% CI 0.56\u20130.88, p = 0.002), but not for patients with ESR1 wildtype (HR = 0.88, 95% CI 0.68\u20131.13, p = 0.32). ER degraders were associated with a significant improvement in PFS in the ITT population, with HR 0.81, 95% CI 0.68\u20130.96, p = 0.02. Significant improvement in PFS was found for patients with an ESR1 mutation (HR 0.55, 95% CI 0.45\u20130.68, p &lt; 0.0001), but not for patients with the ESR1 wildtype (HR 0.97, 95% CI 0.86\u20131.09, p = 0.61. Conclusions: Compared to standard ET, ER degraders were associated with statistically significant improvement in OS and PFS. Subgroup analyses confirmed that the benefit is limited to patients with ESR1 mutations.<\/jats:p>","DOI":"10.3390\/cancers18132077","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T08:43:57Z","timestamp":1782463437000},"page":"2077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Estrogen Receptor Degraders Compared to Standard Endocrine Therapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-4634","authenticated-orcid":false,"given":"Hadar","family":"Goldvaser","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salome","family":"Khutsurauli","sequence":"additional","affiliation":[{"name":"Hillel Yaffe Medical Center, Ha-Shalom St., P.O. Box 169, Hadera 3820302, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Buchinger","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, Shaare Zedek Medical Center, 12 Shmuel Bait, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Safonov","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-5719","authenticated-orcid":false,"given":"Albert","family":"Grinshpun","sequence":"additional","affiliation":[{"name":"The Helmsley Cancer Center, Shaare Zedek Medical Center, 12 Shmuel Bait, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102666","DOI":"10.1016\/j.ctrv.2023.102666","article-title":"Reporting of post-protocol therapies in metastatic breast cancer registration clinical trials: A systematic review","volume":"122","author":"Shachar","year":"2024","journal-title":"Cancer Treat. 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