{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:43:41Z","timestamp":1777671821430,"version":"3.51.4"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI grants","award":["U10CA180888"],"award-info":[{"award-number":["U10CA180888"]}]},{"name":"NCI grants","award":["U10CA180819"],"award-info":[{"award-number":["U10CA180819"]}]},{"name":"NCI grants","award":["U10CA180835"],"award-info":[{"award-number":["U10CA180835"]}]},{"name":"NCI grants","award":["UG1CA232760"],"award-info":[{"award-number":["UG1CA232760"]}]},{"name":"NCI grants","award":["U10CA180863"],"award-info":[{"award-number":["U10CA180863"]}]},{"name":"NCI grants","award":["U10CA063844"],"award-info":[{"award-number":["U10CA063844"]}]},{"name":"NCI grants","award":["UG1CA189953"],"award-info":[{"award-number":["UG1CA189953"]}]},{"name":"NCI grants","award":["UG1CA233340"],"award-info":[{"award-number":["UG1CA233340"]}]},{"name":"NCI grants","award":["UG1CA189971"],"award-info":[{"award-number":["UG1CA189971"]}]},{"name":"NCI grants","award":["UG1CA233329"],"award-info":[{"award-number":["UG1CA233329"]}]},{"name":"NCI grants","award":["UG1CA239767"],"award-info":[{"award-number":["UG1CA239767"]}]},{"name":"NCI grants","award":["UG1CA233337"],"award-info":[{"award-number":["UG1CA233337"]}]},{"name":"NCI grants","award":["U10CA004919"],"award-info":[{"award-number":["U10CA004919"]}]},{"name":"Amgen, Inc. Clinical trial information","award":["NCT00070564"],"award-info":[{"award-number":["NCT00070564"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>S0221 investigated weekly vs every 2\u2009weeks dosing of doxorubicin (A) and cyclophosphamide (C) followed by paclitaxel in patients with high-risk early breast cancer. After an interim analysis, random assignment to the 2 AC arms was stopped for futility, and the trial was modified to study only the paclitaxel schedules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between December 2003 and November 2010, a total of 2716 patients were randomly assigned in a 2 \u00d7 2 factorial design to 15\u2009weeks of weekly A and daily C vs 6 cycles of every 2\u2009weeks AC; and weekly paclitaxel for 12\u2009weeks vs 6 cycles of every 2\u2009weeks paclitaxel. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of every 2\u2009weeks AC and randomly assigned to weekly vs every 2\u2009weeks paclitaxel. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At a median follow-up of 12.1\u2009years, there were no statistically significant differences among the 4 treatment arms in disease-free survival (DFS) (P\u2009=\u2009.91) or overall survival (P\u2009=\u2009.34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomly assigned to paclitaxel weekly vs every 2\u2009weeks paclitaxel, there were no overall differences in DFS (P\u2009=\u2009.32) or overall survival (P\u2009=\u2009.42).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>As there were no statistically significant outcome differences in DFS or overall survival between the studied schedules of AC and paclitaxel with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jncics\/pkag024","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:43:45Z","timestamp":1773330225000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-term follow-up of S0221, comparing alternative dose-schedules of anthracycline and taxane therapy in early breast cancer"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-6664","authenticated-orcid":false,"given":"Azka","family":"Ali","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Cleveland Clinic Foundation, Taussig Cancer Institute , Cleveland, OH,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-2282","authenticated-orcid":false,"given":"William E","family":"Barlow","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washigton, SWOG Statistics and Data Management Center , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7472-9350","authenticated-orcid":false,"given":"Halle C F","family":"Moore","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Cleveland Clinic Foundation, Taussig Cancer Institute , Cleveland, OH,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J","family":"Hobday","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic Comprehensive Cancer Center , Rochester, MN,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9646-1260","authenticated-orcid":false,"given":"Claudine","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Georgetown Lombardi Comprehensive Cancer Center , Washington, DC,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Salim","sequence":"additional","affiliation":[{"name":"Division of Oncology, Allan Blair Cancer Center , Regina, Saskatchewan,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2899-2473","authenticated-orcid":false,"given":"Kathy S","family":"Albain","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Loyola University Chicago, Stritch School of Medicine , Chicago, IL,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8372-1180","authenticated-orcid":false,"given":"Helen K","family":"Chew","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of California-Davis Comprehensive Cancer Center , Sacramento, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary V","family":"Burton","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Louisiana State University Health Sciences Center , Shreveport, LA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3519-0409","authenticated-orcid":false,"given":"Gordan","family":"Srkalovic","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Michigan Health - Sparrow, Herbert-Herman Cancer Center , Lansing, MI,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8298-0289","authenticated-orcid":false,"given":"Bradley A","family":"McGregor","sequence":"additional","affiliation":[{"name":"Dvision of Hematology and Oncology, Dana-Farber Cancer Institute , Boston, MA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2132-902X","authenticated-orcid":false,"given":"Lawrence E","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Karmanos Cancer Institute\/Wayne State University , Detroit, MI,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danika L","family":"Lew","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Washigton, SWOG Statistics and Data Management Center , Seattle, WA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-9928","authenticated-orcid":false,"given":"Julie R","family":"Gralow","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology Association for Clinical Oncology , Alexandria, VA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel N","family":"Hortobagyi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Texas MD Anderson Cancer Center , Houston, TX,","place":["United 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