{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:42:30Z","timestamp":1793065350275,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N002121\/1"],"award-info":[{"award-number":["MR\/N002121\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4\/6 inhibitor (CDK4\/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4\/6i.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PALOMA-3 was a phase III, multicenter, double-blind randomized controlled trial of palbociclib plus fulvestrant (n\u2009=\u2009347) vs placebo plus fulvestrant (n\u2009=\u2009174) in patients with endocrine-pretreated estrogen receptor\u2013positive (ER+) breast cancer. Pretreatment plasma samples from 459 patients were analyzed for mutations in 17 genes, copy number in 14 genes, and circulating tumor fraction. Progression-free survival (PFS) was compared in patients with circulating tumor fraction above or below a prespecified cutoff of 10% and with or without a specific genomic alteration. All statistical tests were 2-sided.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with high ctDNA fraction had worse PFS on both palbociclib plus fulvestrant (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.17 to 2.24; P = .004) and placebo plus fulvestrant (HR = 1.77, 95% CI = 1.21 to 2.59; P = .004). In multivariable analysis, high-circulating tumor fraction was associated with worse PFS (HR = 1.20 per 10% increase in tumor fraction, 95% CI = 1.09 to 1.32; P &amp;lt; .001), as was TP53 mutation (HR = 1.84, 95% CI = 1.27 to 2.65; P = .001) and FGFR1 amplification (HR = 2.91, 95% CI = 1.61 to 5.25; P &amp;lt; .001). No interaction with treatment randomization was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pretreatment ctDNA identified a group of high-risk patients with poor clinical outcome despite the addition of CDK4\/6 inhibition. These patients might benefit from inclusion in future trials of escalating treatment, with therapies that may be active in these genomic contexts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djaa087","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T15:11:01Z","timestamp":1591888261000},"page":"309-317","source":"Crossref","is-referenced-by-count":104,"title":["Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer"],"prefix":"10.1093","volume":"113","author":[{"given":"Ben","family":"O\u2019Leary","sequence":"first","affiliation":[{"name":"Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK"},{"name":"Breast Unit, Royal Marsden Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind J","family":"Cutts","sequence":"additional","affiliation":[{"name":"Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Pfizer, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hrebien","sequence":"additional","affiliation":[{"name":"Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2728-5718","authenticated-orcid":false,"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Pfizer, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut Gustave Roussy, Universit\u00e9 Paris Sud, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Loibl","sequence":"additional","affiliation":[{"name":"German Breast Group, Martin Behaim-Strasse 12, Neu-Isenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherene","family":"Loi","sequence":"additional","affiliation":[{"name":"Division of Research and Cancer Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-7969","authenticated-orcid":false,"given":"Isaac","family":"Garcia-Murillas","sequence":"additional","affiliation":[{"name":"Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, 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