{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:03:41Z","timestamp":1790348621057,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,3,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>SERENA-3 is a presurgical window-of-opportunity (WOO) trial exploring the pharmacodynamic effects of camizestrant in postmenopausal women with newly diagnosed estrogen receptor (ER)\u2013positive, human epidermal growth factor receptor 2\u2013negative breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This open-label, parallel-group trial randomly assigned 132 participants to receive camizestrant 75, 150, or 300 mg once daily for 5-7 days or 75 or 150 mg once daily for 12-15 days. The effects of camizestrant on ER expression, activity, and tumor proliferation were assessed in pre- and on-treatment tumor samples by immunohistochemical (IHC) analysis of ER, progesterone receptor (PgR), and Ki67. Exploratory analyses using transcriptomics and mass spectrometry were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>ER expression was reduced by approximately 65% for all camizestrant doses, regardless of treatment duration. Reduction in Ki67 expression was greater after 12-15 days of camizestrant treatment, compared with 5-7 days. Exploratory analyses including mass spectrometry and IHC image analysis aligned with IHC H-score, indicating equivalent, maximal effects of all tested doses of camizestrant on ER expression and activity and Ki67 expression. Of those participants receiving camizestrant 75 mg once daily, 90%-100% reported no treatment-emergent adverse events across all preferred terms; of those reported, all were Grade 1 except one participant with Grade 2 upper respiratory tract infection, not considered related to camizestrant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>SERENA-3 demonstrates that camizestrant 75 mg once daily (Phase III dose) is well-tolerated and achieves maximal reduction in ER through known mechanisms, that is, antagonism and degradation, by 5-7 days, and proliferation suppression determined by Ki67 expression, by 12-15 days. These data support camizestrant 75 mg once daily as the preferred dose for ongoing clinical development and highlight the importance of presurgical WOO studies in guiding dose selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01548","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T20:59:08Z","timestamp":1768597148000},"page":"750-761","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacodynamics of Camizestrant Treatment in Postmenopausal Women With Estrogen Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative Primary Breast Cancer: Results From the Randomized, Presurgical SERENA-3 Study"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct04588298","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6212-3979","authenticated-orcid":true,"given":"John F.R.","family":"Robertson","sequence":"first","affiliation":[{"name":"University Hospitals of Derby and Burton, Royal Derby Hospital, Derby, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teimuraz","family":"Gogitidze","sequence":"additional","affiliation":[{"name":"LTD Brothers, Batumi, Ajaria, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaza","family":"Katashvili","sequence":"additional","affiliation":[{"name":"Acad. 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