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

Fu Z, Borho L, Taylor SE, Kelemen LE, DeFazio A, Webb PM, Köbel M, Meagher NS, Na R, Antoniou AC, Brand AH, Kennedy CJ, Nevins N, Pharoah PD, Shvetsov YB, Winham SJ, Alsop J, Beckmann M, Bolithon A, Boros J, Bowtell DD, Brenton JD, Carney ME, Chudecka-Głaz A, Cook LS, Cybulski C, Fasching P, Fereday S, Fortner RT, García MJ, Goode EL, Goodman MT, Gronwald J, Hartmann A, Hernandez BY, Høgdall E, Huntsman DG, Jensen A, Jimenez-Linan M, Joseph JM, Karlan BY, Kaznowska E, Kjaer SK, Kluz T, Koziak JM, Lester J, Longacre TA, Lycke M, McGuire V, Moysich KB, Murphy RA, Orsulic S, Ramus SJ, Rodríguez-Antona C, Rothstein JH, Samra S, Sieh W, Steed H, Sundfeldt K, Talhouk A, Uciński J, Wang C, Wentzensen N, Whittemore AS, Wilkens LR, Songer T, Brooks MM, Tang L, Modugno F (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 198

Pages Range: 112-129

DOI: 10.1016/j.ygyno.2025.05.013

Abstract

Objective: Many 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. Method: We 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. Results: Overweight/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 (Pheter=0.003). Postmenopause was associated with a higher risk of PR- tumors (OR 1.52, 95 % CI 1.26–1.83), which varied based by AR (Pheter < 0.001) and ER (Pheter < 0.001) expression. Gravidity, oral contraception duration, and breastfeeding duration showed differing dose-response relationships according to AR/ER/PR expression. Hormone therapy use, postmenopause, physical inactivity, and being obese/overweight prior to diagnosis were differentially associated with survival based on AR/ER/PR expression and histotype. Conclusion: EOC 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.

Authors with CRIS profile

Involved external institutions

Uniwersytet Rzeszowski Poland (PL) University of California Los Angeles (UCLA) United States (USA) (US) Stanford University United States (USA) (US) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Roswell Park Cancer Institute United States (USA) (US) University of British Columbia Canada (CA) University of Pittsburgh United States (USA) (US) South Carolina Department of Mental Health United States (USA) (US) University of New South Wales (UNSW) Australia (AU) University of Texas MD Anderson Cancer Center United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Westmead Institute for Medical Research Australia (AU) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Calgary Canada (CA) University of Sydney (USYD) Australia (AU) University of Cambridge United Kingdom (GB) Cedars-Sinai Medical Center United States (USA) (US) Mayo Clinic United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Colorado Anschutz Medical Campus United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Instituto de Investigaciones Biomédicas Alberto Sols (IIBM) Spain (ES) University of Alberta Canada (CA) University of Gothenburg / Göteborgs universitet Sweden (SE) National Cancer Institute (NCI) United States (USA) (US) Gentofte Hospital Denmark (DK) Danish Cancer Society Research Center Denmark (DK) Addenbrooke's Hospital United Kingdom (GB)

How to cite

APA:

Fu, Z., Borho, L., Taylor, S.E., Kelemen, L.E., DeFazio, A., Webb, P.M.,... Modugno, F. (2025). 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. Gynecologic Oncology, 198, 112-129. https://doi.org/10.1016/j.ygyno.2025.05.013

MLA:

Fu, Zhuxuan, et al. "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." Gynecologic Oncology 198 (2025): 112-129.

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