{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T08:13:36Z","timestamp":1770884016840,"version":"3.50.1"},"reference-count":32,"publisher":"American Association for Cancer Research (AACR)","issue":"4","funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001073"],"award-info":[{"award-number":["UL1 TR001073"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1 TR001072"],"award-info":[{"award-number":["TL1 TR001072"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2 TR001071"],"award-info":[{"award-number":["KL2 TR001071"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1R01CA133010"],"award-info":[{"award-number":["1R01CA133010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10 CA27469"],"award-info":[{"award-number":["U10 CA27469"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gynecologic Oncology Group Statistical and Data Center","award":["U10 CA180822"],"award-info":[{"award-number":["U10 CA180822"]}]},{"name":"Gynecologic Oncology Group Tissue Bank","award":["U24 CA114796"],"award-info":[{"award-number":["U24 CA114796"]}]},{"DOI":"10.13039\/100018047","name":"NRG Oncology","doi-asserted-by":"crossref","award":["U24 CA196067"],"award-info":[{"award-number":["U24 CA196067"]}],"id":[{"id":"10.13039\/100018047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>The influence of sex hormone and insulin\/insulin-like growth factor (IGF) axis signaling on endometrial cancer recurrence is unknown. We evaluated these pathways in a prospective cohort of Gynecologic Oncology Group (GOG)0210 trial endometrial adenocarcinoma patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>Stage II\u2013IV patients (N = 816) were included in this study. Pretreatment specimens were tested for tumor mRNA and protein expression of IGF1, IGF2, IGF-binding proteins (IGFBP)-1 and -3, insulin (IR) and IGF-I receptors (IGF1R), phosphorylated IR\/IGF1R (pIGF1R\/pIR), and estrogen (ER) and progesterone receptors (PR) using qPCR and IHC. Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone, and sex hormone binding globulin were measured. HRs and 95% confidence intervals (CI) for progression-free survival were calculated from Cox models adjusting for age, stage, and grade.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Recurrence occurred in 280 (34%) cases during a median of 4.6 years of follow-up. ER positivity (HR, 0.67; 95% CI, 0.47\u20130.95), IR positivity (HR, 0.53; 95% CI, 0.29\u20130.98), and circulating IGF-I (highest vs. lowest quartile: HR, 0.66; 95% CI, 0.47\u20130.92) were inversely associated with recurrence risk. Circulating estradiol (highest vs. lowest tertile: HR, 1.55; 95% CI, 1.02\u20132.36) and pIGF1R\/pIR positivity (HR, 1.40; 95% CI, 1.02\u20131.92) were associated with increased recurrence risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Circulating estradiol and tumor tissue phosphorylated (activated) IGR1R\/IR were independently associated with higher risk of recurrence in patients with endometrial cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Impact:<\/jats:title>\n                  <jats:p>This study may inform future clinical trials of endocrine-targeted adjuvant therapies in patients with endometrial cancer that could include baseline assessment of serum and tissue biomarkers of estradiol and insulin signaling pathways.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1158\/1055-9965.epi-20-1613","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T18:15:16Z","timestamp":1614104116000},"page":"719-726","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sex Hormones, Insulin, and Insulin-like Growth Factors in Recurrence of High-Stage Endometrial Cancer"],"prefix":"10.1158","volume":"30","author":[{"given":"Melissa A.","family":"Merritt","sequence":"first","affiliation":[{"name":"1Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii."}]},{"given":"Howard D.","family":"Strickler","sequence":"additional","affiliation":[{"name":"2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, New York."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7353-5650","authenticated-orcid":false,"given":"Alan D.","family":"Hutson","sequence":"additional","affiliation":[{"name":"3Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York."}]},{"given":"Mark H.","family":"Einstein","sequence":"additional","affiliation":[{"name":"4Department of Obstetrics, Gynecology & Women's Health, Rutgers New Jersey Medical School, Newark, New Jersey."}]},{"given":"Thomas E.","family":"Rohan","sequence":"additional","affiliation":[{"name":"2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, New York."}]},{"given":"Xiaonan","family":"Xue","sequence":"additional","affiliation":[{"name":"2Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, New York."}]},{"given":"Mark E.","family":"Sherman","sequence":"additional","affiliation":[{"name":"5Mayo Clinic College of Medicine, Jacksonville, Florida."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-8562","authenticated-orcid":false,"given":"Louise A.","family":"Brinton","sequence":"additional","affiliation":[{"name":"6Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland."}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-4815","authenticated-orcid":false,"given":"Herbert","family":"Yu","sequence":"additional","affiliation":[{"name":"1Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-5887","authenticated-orcid":false,"given":"David S.","family":"Miller","sequence":"additional","affiliation":[{"name":"7Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas."}]},{"given":"Nilsa C.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"8Nationwide Children's Hospital, Columbus, Ohio."}]},{"given":"Heather A.","family":"Lankes","sequence":"additional","affiliation":[{"name":"9NRG Oncology\/Operations Center-Philadelphia East, Philadelphia, Pennsylvania."},{"name":"10Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, Columbus, Ohio."}]},{"given":"Michael J.","family":"Birrer","sequence":"additional","affiliation":[{"name":"11Winthrop P. 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