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. 2025 Jul:198:112-129.
doi: 10.1016/j.ygyno.2025.05.013. Epub 2025 Jun 6.

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

Zhuxuan Fu  1 Lauren Borho  2 Sarah E Taylor  2 Linda E Kelemen  3 Anna DeFazio  4 Penelope M Webb  5 Martin Köbel  6 Nicola S Meagher  7 Renhua Na  5 Antonis C Antoniou  8 Alison H Brand  9 Catherine J Kennedy  10 Nikilyn Nevins  10 Paul D P Pharoah  11 Yurii B Shvetsov  12 Stacey J Winham  13 Jennifer Alsop  14 Matthias W Beckmann  15 Adelyn Bolithon  16 Jessica Boros  10 David D L Bowtell  17 James D Brenton  18 Michael E Carney  19 Anita Chudecka-Głaz  20 Linda S Cook  21 Cezary Cybulski  22 Peter A Fasching  15 Sian Fereday  17 Renée T Fortner  23 María J García  24 Ellen L Goode  25 Marc T Goodman  26 Jacek Gronwald  27 Arndt Hartmann  15 Brenda Y Hernandez  12 Estrid Høgdall  28 David G Huntsman  29 Allan Jensen  30 Mercedes Jimenez-Linan  31 Janine M Joseph  32 Beth Y Karlan  33 Ewa Kaznowska  34 Susanne K Kjaer  35 Tomasz Kluz  36 Jennifer M Koziak  37 Jenny Lester  33 Teri A Longacre  38 Maria Lycke  39 Valerie McGuire  40 Kirsten B Moysich  32 Rachel A Murphy  41 Sandra Orsulic  33 Susan J Ramus  16 Cristina Rodríguez-Antona  42 Joseph H Rothstein  43 Spinder Samra  44 Weiva Sieh  45 Helen Steed  46 Karin Sundfeldt  47 Aline Talhouk  48 Jan Uciński  20 Chen Wang  13 Nicolas Wentzensen  49 Alice S Whittemore  50 Lynne R Wilkens  12 Thomas Songer  51 Maria Mori Brooks  51 Lu Tang  52 Francesmary Modugno  53
Affiliations

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

Zhuxuan Fu et al. Gynecol Oncol. 2025 Jul.

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.

Keywords: Epithelial ovarian cancer; Hormonal factors; Hormone receptor; Risk; Survival; androgen receptor; estrogen receptor; progesterone receptor.

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Conflict of interest statement

Declaration of competing interest Jessica Boros: Cancer Institute New South Wales, National Health and Medical Research Council of Australia, Department of Gynecological Oncology, Westmead Hospital, NSW, The Westmead Institute for Medical Research. Alison Brand: Board of Directors of ANZGOG and GCIG, Data Safety Management Board for DEBULK. Anna DeFazio: Research support from AstraZeneca, Illumina. Sian Fereday: AstraZeneca Pty Ltd. – Research Grant to AOCS. Maria J. Garcia: Proyect Grant from Ministerio de Ciencia, Innovación y Universidades. Ellen Goode: Mayo Foundation; Minnesota. Arndt Hartmann: AstraZeneca, Biocartis, Cepheid, Gilead, Illumina, Janssen, Novartis, Owkin, Qiagen, QUIP GmbH – payments to the institution. Beth Karlan: American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN); UCLA Clinical and Translational Science Institute – Precision Health; Independent Data Monitoring Committee – GRAIL PATHFINDER; Scientific Advisor to Ovarian Cancer Research Alliance (OCRA) and American Cancer Society (ACS) BrightEdge. Catherine Jane Kennedy: Australian National Health and Medical Research Council, Cancer Institute NSW – grant payments to my institution. Martin Kobel: Payments from Astra Zeneca, GSK, Merck, AbbVie, Helix biopharma. Renhua Na: NHMRC Program Grant (GNT1073898). Niklyn Nevins: Research support from Illumina. Christina Rodriguez-Antona: Grant PID2021-1283120B-100, funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. Penelope M. Webb: U.S. Army Medical Research and Material Command, National Health & Medical Research Council of Australia, Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania and Cancer Foundation of Western Australia – Grants to institution. All other authors declare no conflicts of interest.

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