ArticleGynecologic oncology2025
Ovarian cancer risk and survival according to tumor sex hormone receptor expression: An ovarian Cancer association consortium and ovarian tumor tissue analysis consortium pooled analysis.
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69 authors.
Zhuxuan FuDepartment of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA 15213, USA; St. Luke's Mid America Heart Institute. St Luke's Health System. Kansas City, MO, USA.
Lauren BorhoDivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences. University of Pittsburgh School of Medicine. Pittsburgh, PA 15213, USA.
Sarah E TaylorDivision of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences. University of Pittsburgh School of Medicine. Pittsburgh, PA 15213, USA.
Linda E KelemenSouth Carolina Department of Public Health. Columbia, SC, USA.
Anna DeFazioCentre for Cancer Research. The Westmead Institute for Medical Research. Sydney, New South Wales 2145, Australia; Faculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Gynaecological Oncology. Westmead Hospital. Sydney, New South Wales 2145, Australia; The Daffodil Centre, The University of Sydney. A Joint Venture with Cancer Council NSW. Sydney, New South Wales 2006, Australia.
Penelope M WebbPopulation Health Program. QIMR Berghofer. Brisbane, Queensland 4006, Australia; School of Public Health. The University of Queensland. Brisbane 4006, Australia.
Martin KöbelDepartment of Pathology and Laboratory Medicine. University of Calgary, Foothills Medical Center. Calgary, AB T2N 2T9, Canada.
Nicola S MeagherThe Daffodil Centre, The University of Sydney. A Joint Venture with Cancer Council NSW. Sydney, New South Wales 2006, Australia; School of Clinical Medicine, UNSW Medicine and Health. University of NSW Sydney. Sydney, New South Wales 2052, Australia.
Renhua NaPopulation Health Program. QIMR Berghofer. Brisbane, Queensland 4006, Australia; School of Public Health. The University of Queensland. Brisbane 4006, Australia.
Antonis C AntoniouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care. University of Cambridge. Cambridge CB1 8RN, UK.
Alison H BrandFaculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Gynaecological Oncology. Westmead Hospital. Sydney, New South Wales 2145, Australia.
Catherine J KennedyCentre for Cancer Research. The Westmead Institute for Medical Research. Sydney, New South Wales 2145, Australia; Faculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Gynaecological Oncology. Westmead Hospital. Sydney, New South Wales 2145, Australia.
Nikilyn NevinsCentre for Cancer Research. The Westmead Institute for Medical Research. Sydney, New South Wales 2145, Australia; Faculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Gynaecological Oncology. Westmead Hospital. Sydney, New South Wales 2145, Australia.
Paul D P PharoahDepartment of Computational Biomedicine. Cedars-Sinai Medical Center. West Hollywood, CA 90069, USA.
Yurii B ShvetsovUniversity of Hawaii Cancer Center. Honolulu, HI, USA.
Stacey J WinhamDepartment of Quantitative Health Sciences, Division of Computational Biology. Mayo Clinic. Rochester, MN 55905, USA.
Jennifer AlsopCenter for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
Matthias W BeckmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg. University Hospital Erlangen. Erlangen 91054, Germany.
Adelyn BolithonSchool of Clinical Medicine, UNSW Medicine and Health. University of NSW Sydney. Sydney, New South Wales 2052, Australia; Adult Cancer Program, Lowy Cancer Research Centre. University of NSW Sydney. Sydney, New South Wales 2052, Australia.
Jessica BorosCentre for Cancer Research. The Westmead Institute for Medical Research. Sydney, New South Wales 2145, Australia; Faculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Gynaecological Oncology. Westmead Hospital. Sydney, New South Wales 2145, Australia.
David D L BowtellPeter MacCallum Cancer Centre. Melbourne, Victoria 3000, Australia; Sir Peter MacCallum Department of Oncology. The University of Melbourne. Parkville, Victoria 3010, Australia.
James D BrentonCancer Research UK Cambridge Institute, University of Cambridge. Cambridge CB2 0RE, UK.
Michael E CarneyDepartment of Obstetrics and Gynecology, John A. Burns School of Medicine. University of Hawaii. Honolulu, HI, USA.
Anita Chudecka-GłazDepartment of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents. Pomeranian Medical University. Szczecin 70-111, Poland.
Linda S CookEpidemiology, School of Public Health, University of Colorado. Aurora, CO, USA; Community Health Sciences. University of Calgary. Calgary, AB, Canada.
Cezary CybulskiInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg. University Hospital Erlangen. Erlangen 91054, Germany.
Sian FeredayPeter MacCallum Cancer Centre. Melbourne, Victoria 3000, Australia; Sir Peter MacCallum Department of Oncology. The University of Melbourne. Parkville, Victoria 3010, Australia.
Renée T FortnerDivision of Cancer Epidemiology. German Cancer Research Center (DKFZ). Heidelberg 69120, Germany; Department of Research, Cancer Registry of Norway. Norwegian Institute of Public Health. Oslo, Norway.
María J GarcíaGenomic Biomarkers and Precision Oncology Laboratory, Cancer Department. Sols-Morreale Biomedical Research Institute (IIBM), CSIC-UAM. Madrid, Spain.
Ellen L GoodeDepartment of Quantitative Health Sciences, Division of Epidemiology. Mayo Clinic. Rochester, MN 55905, USA.
Marc T GoodmanCancer Prevention and Control Program, Cedars-Sinai Cancer. Cedars-Sinai Medical Center. Los Angeles, CA 90048, USA.
Jacek GronwaldDepartment of Genetics and Pathology. Pomeranian Medical University. Szczecin 71-252, Poland.
Arndt HartmannDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg. University Hospital Erlangen. Erlangen 91054, Germany.
Brenda Y HernandezUniversity of Hawaii Cancer Center. Honolulu, HI, USA.
Estrid HøgdallDepartment of Pathology, Herlev Hospital. University of Copenhagen. Copenhagen DK-2100, Denmark.
David G HuntsmanDepartment of Obstetrics and Gynecology. University of British Columbia. Vancouver, BC V5Z 1L3, Canada; Department of Molecular Oncology. BC Cancer Research Centre. Vancouver, BC V5Z 4E6, Canada.
Allan JensenDepartment of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen DK-2100, Denmark.
Mercedes Jimenez-LinanDepartment of Histopathology. Addenbrooke's Hospital. Cambridge, UK.
Janine M JosephDepartment of Cancer Prevention and Control. Roswell Park Comprehensive Cancer Center. Buffalo, NY 14263, USA.
Beth Y KarlanDavid Geffen School of Medicine, Department of Obstetrics and Gynecology. University of California at Los Angeles. Los Angeles, CA 90095, USA.
Ewa KaznowskaDepartment of Pathology, Faculty of Medicine, University of Rzeszow. 35-559 Rzesow, Poland.
Susanne K KjaerDepartment of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen DK-2100, Denmark; Department of Gynaecology, Rigshospitalet. University of Copenhagen. Copenhagen DK-2100, Denmark.
Tomasz KluzDepartment of Gynecology, Gynecology Oncology and Obstetrics. Institute of Medical Sciences, Medical College of Rzeszow University. Rzesz-w: Poland.
Jennifer M KoziakDepartment of Obstetrics and Gynaecology. University of Calgary. Calgary, AB, Canada.
Jenny LesterDavid Geffen School of Medicine, Department of Obstetrics and Gynecology. University of California at Los Angeles. Los Angeles, CA 90095, USA.
Teri A LongacreDepartment of Pathology. Stanford University School of Medicine. Stanford, CA 94305, USA.
Maria LyckeDepartment of Obstetrics and Gynecology, Institute of Clinical Science. Sahlgrenska University hospital, University of Gothenburg. Gothenburg: Sweden.
Valerie McGuireDepartment of Epidemiology and Population Health. Stanford University School of Medicine. Stanford, CA 94305, USA; Department of Epidemiology and Biostatistics. University of California San Francisco. San Francisco, CA 94158, USA.
Kirsten B MoysichDepartment of Cancer Prevention and Control. Roswell Park Comprehensive Cancer Center. Buffalo, NY 14263, USA.
Rachel A MurphySchool of Population and Public Health. University of British Columbia. Vancouver, BC V6T 1Z4, Canada; Cancer Control Research. BC Cancer Agency. Vancouver, BC V5Z 1L3, Canada.
Sandra OrsulicDavid Geffen School of Medicine, Department of Obstetrics and Gynecology. University of California at Los Angeles. Los Angeles, CA 90095, USA.
Susan J RamusSchool of Clinical Medicine, UNSW Medicine and Health. University of NSW Sydney. Sydney, New South Wales 2052, Australia; Adult Cancer Program, Lowy Cancer Research Centre. University of NSW Sydney. Sydney, New South Wales 2052, Australia.
Cristina Rodríguez-AntonaPharmacogenomics and Tumour Biomarkers Laboratory, Cancer Department. Sols-Morreale Biomedical Research Institute (IIBM), CSIC-UAM. Madrid, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III. Madrid 28029, Spain.
Joseph H RothsteinDepartment of Epidemiology. University of Texas MD Anderson Cancer Center. Houston, TX 77030, USA; Department of Population Health Science and Policy. Icahn School of Medicine at Mount Sinai. New York, NY 10029, USA.
Spinder SamraFaculty of Medicine and Health. The University of Sydney. Sydney, New South Wales 2006, Australia.; Department of Tissue Pathology and Diagnostic Oncology, ICPMR West Mead Hospital, New South Wales, Australia.
Weiva SiehDepartment of Epidemiology. University of Texas MD Anderson Cancer Center. Houston, TX 77030, USA; Department of Genetics and Genomic Sciences. Icahn School of Medicine at Mount Sinai. New York, NY 10029, USA.
Helen SteedDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology. University of Alberta. Edmonton, Alberta T5H 3V9, Canada; Section of Gynecologic Oncology Surgery, North Zone. Alberta Health Services. Edmonton, Alberta, Canada.
Karin SundfeldtDepartment of Obstetrics and Gynecology, Institute of Clinical Science, Sahlgrenska Center for Cancer Research. University of Gothenburg. Gothenburg, Sweden.
Aline TalhoukDepartment of Obstetrics and Gynecology. University of British Columbia. Vancouver, BC V5Z 1L3, Canada; British Columbia's Gynecological Cancer Research Team (OVCARE). University of British Columbia, BC Cancer, and Vancouver General Hospital. Vancouver, BC V5Z 4E6, Canada.
Jan UcińskiDepartment of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents. Pomeranian Medical University. Szczecin 70-111, Poland.
Chen WangDepartment of Quantitative Health Sciences, Division of Computational Biology. Mayo Clinic. Rochester, MN 55905, USA.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics. National Cancer Institute. Bethesda, MD 20892, USA.
Alice S WhittemoreDepartment of Epidemiology and Population Health. Stanford University School of Medicine. Stanford, CA 94305, USA; Department of Biomedical Data Science. Stanford University School of Medicine. Stanford, CA 94305, USA.
Lynne R WilkensUniversity of Hawaii Cancer Center. Honolulu, HI, USA.
Thomas SongerDepartment of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA 15213, USA.
Maria Mori BrooksDepartment of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA 15213, USA.
Lu TangDepartment of Biostatistics. University of Pittsburgh Graduate School of Public Health. Pittsburgh, PA, USA.
Francesmary ModugnoDepartment of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA 15213, USA; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences. University of Pittsburgh School of Medicine. Pittsburgh, PA 15213, USA; Women's Cancer Research Center. Magee-Womens Research Institute and Hillman Cancer Center. Pittsburgh 15213, PA, USA; Department of Biomedical Informatics. University of Pittsburgh School of Medicine. Pittsburgh, PA 15213, USA. Electronic address: modugnof@upmc.edu.
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MUniversity of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GERTRAUD MASKARINEC · 1996 to 2026
$56.2MUse of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0MWITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2MNorthern California Cooperative Family Registry for Breast CancerU01CA069417 · NCI · NORTHERN CALIFORNIA CANCER CENTER · PI JOHN, ESTHER M. · 1995 to 2010
$22.4MProject 3: Hedgehog Inhibition to Enhance Response to ICI TherapyP50CA272218 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ronald J Buckanovich, Robert Page Edwards · 2023 to 2026
$11.0MRelating Molecular Subgroups of Endometriosis-Associated Ovarian Cancers to Survival and RiskR01CA248288 · NCI · MAYO CLINIC ROCHESTER · PI Stacey J Winham · 2021 to 2026
$4.8MCOLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPSR01CA058598 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI GOODMAN, MARC T · 1993 to 2012
$4.6MInflammation and Ovarian CancerR01CA095023 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BUNKER, CLAREANN H. · 2003 to 2008
$2.7MGenetic Variation in the NF-kappaB Pathway and Ovarian Cancer EtiologyR01CA122443 · NCI · MAYO CLINIC ROCHESTER · PI GOODE, ELLEN L. · 2007 to 2012
$2.7MMitochondrial DNA and Ovarian Cancer Risk and SurvivalR01CA160669 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI COOK, LINDA S · 2012 to 2016
$2.2MCancer Research UK C490/A16561NCATS NIH HHS UL1 TR000124NCI NIH HHS K07 CA080668NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA071789NCI NIH HHS P50 CA136393NCI NIH HHS P50 CA272218NCI NIH HHS R01 CA058598NCI NIH HHS R01 CA095023NCI NIH HHS R01 CA122443NCI NIH HHS R01 CA160669NCI NIH HHS R01 CA248288NCI NIH HHS R03 CA092776NCI NIH HHS R21 CA267050NCI NIH HHS U01 CA069417NCRR NIH HHS M01 RR000056
Abstract
objectiveMany epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.
methodWe linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and by histotype using Kaplan-Meier curves and Cox proportional hazards models.
resultsOverweight/obesity was associated with higher risk of ER- tumors (OR:1.53, 95 % I:1.18-1.98). Hysterectomy was associated with greater risk of ER+ tumors (OR:4.99, 95 % CI:4.27-5.83), which varied by AR expression (P
conclusionEOC has varying risk and prognostic profiles depending on both histotype and AR/ER/PR expression. Biological mechanisms underlying the association between hormonally-linked factors and EOC need to be studied by both histotypes and by AR, ER, and PR expression.
Indexed as
Estrogen Receptor alphaNeoplasms, Glandular and EpithelialOvarian NeoplasmsReceptors, AndrogenReceptors, EstrogenReceptors, ProgesteroneAdultAgedCarcinoma, Ovarian EpithelialCase-Control StudiesFemaleHumansMiddle AgedObesityRisk FactorsAR protein, humanEstrogen Receptor alphaReceptors, AndrogenReceptors, EstrogenReceptors, Progesteroneandrogen receptorEpithelial ovarian cancerestrogen receptorHormonal factorsHormone receptorprogesterone receptorRiskSurvival
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