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; Lauren Borho; Sarah E. Taylor; Linda E. Kelemen; Anna DeFazio; Penelope M. Webb; Martin Köbel; Nicola S. Meagher; Renhua Na; Antonis C. Antoniou; Alison H. Brand; Catherine J. Kennedy; Nikilyn Nevins; Paul D.P. Pharoah; Yurii B. Shvetsov; Stacey J. Winham; Jennifer Alsop; Matthias W. Beckmann; Adelyn Bolithon; Jessica Boros; David D.L. Bowtell; James D. Brenton; Michael E. Carney; Anita Chudecka-Głaz; Linda S. Cook; Cezary Cybulski; Peter A. Fasching; Sian Fereday; Renée T. Fortner; María J. García; Ellen L. Goode; Marc T. Goodman; Jacek Gronwald; Arndt Hartmann; Brenda Y. Hernandez; Estrid Høgdall; David G. Huntsman; Allan Jensen; Mercedes Jimenez-Linan; Janine M. Joseph; Beth Y. Karlan; Ewa Kaznowska; Susanne K. Kjaer; Tomasz Kluz; Jennifer M. Koziak; Jenny Lester; Teri A. Longacre; Maria Lycke; Valerie McGuire; Kirsten B. Moysich; Rachel A. Murphy; Sandra Orsulic; Susan J. Ramus; Cristina Rodríguez-Antona; Joseph H. Rothstein; Spinder Samra; Weiva Sieh; Helen Steed; Karin Sundfeldt; Aline Talhouk; Jan Uciński; Chen Wang; Nicolas Wentzensen; Alice S. Whittemore; Lynne R. Wilkens; Thomas Songer; Maria Mori Brooks; Lu Tang; Francesmary Modugno

doi:10.1016/j.ygyno.2025.05.013

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
, Lauren Borho
, Sarah E. Taylor
, Linda E. Kelemen
, Anna DeFazio
, Penelope M. Webb
, Martin Köbel
, Nicola S. Meagher
, Renhua Na
, Antonis C. Antoniou
, Alison H. Brand
, Catherine J. Kennedy
, Nikilyn Nevins
, Paul D.P. Pharoah
, Yurii B. Shvetsov
, Stacey J. Winham
, Jennifer Alsop
, Matthias W. Beckmann
, Adelyn Bolithon
, Jessica Boros

David D.L. Bowtell, James D. Brenton, Michael E. Carney, Anita Chudecka-Głaz, Linda S. Cook, Cezary Cybulski, Peter A. Fasching, Sian Fereday, Renée T. Fortner, María J. García, Ellen L. Goode, Marc T. Goodman, Jacek Gronwald, Arndt Hartmann, Brenda Y. Hernandez, Estrid Høgdall, David G. Huntsman, Allan Jensen, Mercedes Jimenez-Linan, Janine M. Joseph, Beth Y. Karlan, Ewa Kaznowska, Susanne K. Kjaer, Tomasz Kluz, Jennifer M. Koziak, Jenny Lester, Teri A. Longacre, Maria Lycke, Valerie McGuire, Kirsten B. Moysich, Rachel A. Murphy, Sandra Orsulic, Susan J. Ramus, Cristina Rodríguez-Antona, Joseph H. Rothstein, Spinder Samra, Weiva Sieh, Helen Steed, Karin Sundfeldt, Aline Talhouk, Jan Uciński, Chen Wang, Nicolas Wentzensen, Alice S. Whittemore, Lynne R. Wilkens, Thomas Songer, Maria Mori Brooks, Lu Tang, Francesmary Modugno

Department of Epidemiology and Environmental Health

University of Pittsburgh
St Luke Hospital Kansas City
South Carolina Department of Public Health
The Westmead Institute for Medical Research
The University of Sydney
Westmead Hospital
Queensland Institute of Medical Research
University of Queensland
University of Calgary
University of New South Wales
University of Cambridge
Cedars-Sinai Medical Center
University of Hawai'i at Mānoa
Mayo Clinic Rochester, MN
Friedrich-Alexander University Erlangen-Nürnberg
Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre
Peter Maccallum Cancer Centre
University of Melbourne
Cancer Research UK Cambridge Institute
Pomeranian Medical University in Szczecin
Colorado School of Public Health
German Cancer Research Center
Cancer Registry of Norway Institute of Population-Based Cancer Research
CSIC-UAM - Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM)
University of Copenhagen
University of British Columbia
Provincial Health Services Authority
Danish Cancer Institute
Cambridge University Hospitals NHS Foundation Trust
Roswell Park Cancer Institute
University of California at Los Angeles
University of Rzeszów
Medical College of Rzeszow University
Stanford University
Sahlgrenska University Hospital
University of California at San Francisco
AvMonforte de Lemos
University of Texas MD Anderson Cancer Center
Icahn School of Medicine at Mount Sinai
ICPMR West Mead Hospital
University of Alberta
Alberta Health Services
University of Gothenburg
National Institutes of Health

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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 (P_heter=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 (P_heter < 0.001) and ER (P_heter < 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.

Original language	English
Pages (from-to)	112-129
Number of pages	18
Journal	Gynecologic Oncology
Volume	198
DOIs	https://doi.org/10.1016/j.ygyno.2025.05.013
State	Published - Jul 2025

Keywords

Epithelial ovarian cancer
Hormonal factors
Hormone receptor
Risk
Survival
androgen receptor
estrogen receptor
progesterone receptor

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10.1016/j.ygyno.2025.05.013

Cite this

Fu, Z., Borho, L., Taylor, S. E., Kelemen, L. E., DeFazio, A., Webb, P. M., Köbel, M., Meagher, N. S., Na, R., Antoniou, A. C., Brand, A. H., Kennedy, C. J., Nevins, N., Pharoah, P. D. P., Shvetsov, Y. B., Winham, S. J., Alsop, J., Beckmann, M. W., Bolithon, A., ... 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

@article{44c5022ba3194f298d16a8444644818e,

title = "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",

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",

author = "Zhuxuan Fu and Lauren Borho and Taylor, \{Sarah E.\} and Kelemen, \{Linda E.\} and Anna DeFazio and Webb, \{Penelope M.\} and Martin K{\"o}bel and Meagher, \{Nicola S.\} and Renhua Na and Antoniou, \{Antonis C.\} and Brand, \{Alison H.\} and Kennedy, \{Catherine J.\} and Nikilyn Nevins and Pharoah, \{Paul D.P.\} and Shvetsov, \{Yurii B.\} and Winham, \{Stacey J.\} and Jennifer Alsop and Beckmann, \{Matthias W.\} and Adelyn Bolithon and Jessica Boros and Bowtell, \{David D.L.\} and Brenton, \{James D.\} and Carney, \{Michael E.\} and Anita Chudecka-G{\l}az and Cook, \{Linda S.\} and Cezary Cybulski and Fasching, \{Peter A.\} and Sian Fereday and Fortner, \{Ren{\'e}e T.\} and Garc{\'i}a, \{Mar{\'i}a J.\} and Goode, \{Ellen L.\} and Goodman, \{Marc T.\} and Jacek Gronwald and Arndt Hartmann and Hernandez, \{Brenda Y.\} and Estrid H{\o}gdall and Huntsman, \{David G.\} and Allan Jensen and Mercedes Jimenez-Linan and Joseph, \{Janine M.\} and Karlan, \{Beth Y.\} and Ewa Kaznowska and Kjaer, \{Susanne K.\} and Tomasz Kluz and Koziak, \{Jennifer M.\} and Jenny Lester and Longacre, \{Teri A.\} and Maria Lycke and Valerie McGuire and Moysich, \{Kirsten B.\} and Murphy, \{Rachel A.\} and Sandra Orsulic and Ramus, \{Susan J.\} and Cristina Rodr{\'i}guez-Antona and Rothstein, \{Joseph H.\} and Spinder Samra and Weiva Sieh and Helen Steed and Karin Sundfeldt and Aline Talhouk and Jan Uci{\'n}ski and Chen Wang and Nicolas Wentzensen and Whittemore, \{Alice S.\} and Wilkens, \{Lynne R.\} and Thomas Songer and Brooks, \{Maria Mori\} and Lu Tang and Francesmary Modugno",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Inc.",

year = "2025",

month = jul,

doi = "10.1016/j.ygyno.2025.05.013",

language = "English",

volume = "198",

pages = "112--129",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

}

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, PDP, Shvetsov, YB, Winham, SJ, Alsop, J, Beckmann, MW, Bolithon, A, Boros, J, Bowtell, DDL, Brenton, JD, Carney, ME, Chudecka-Głaz, A, Cook, LS, Cybulski, C, Fasching, PA, 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, '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, vol. 198, pp. 112-129. https://doi.org/10.1016/j.ygyno.2025.05.013

TY - JOUR

T1 - Ovarian cancer risk and survival according to tumor sex hormone receptor expression

T2 - An ovarian Cancer association consortium and ovarian tumor tissue analysis consortium pooled analysis

AU - Fu, Zhuxuan

AU - Borho, Lauren

AU - Taylor, Sarah E.

AU - Kelemen, Linda E.

AU - DeFazio, Anna

AU - Webb, Penelope M.

AU - Köbel, Martin

AU - Meagher, Nicola S.

AU - Na, Renhua

AU - Antoniou, Antonis C.

AU - Brand, Alison H.

AU - Kennedy, Catherine J.

AU - Nevins, Nikilyn

AU - Pharoah, Paul D.P.

AU - Shvetsov, Yurii B.

AU - Winham, Stacey J.

AU - Alsop, Jennifer

AU - Beckmann, Matthias W.

AU - Bolithon, Adelyn

AU - Boros, Jessica

AU - Bowtell, David D.L.

AU - Brenton, James D.

AU - Carney, Michael E.

AU - Chudecka-Głaz, Anita

AU - Cook, Linda S.

AU - Cybulski, Cezary

AU - Fasching, Peter A.

AU - Fereday, Sian

AU - Fortner, Renée T.

AU - García, María J.

AU - Goode, Ellen L.

AU - Goodman, Marc T.

AU - Gronwald, Jacek

AU - Hartmann, Arndt

AU - Hernandez, Brenda Y.

AU - Høgdall, Estrid

AU - Huntsman, David G.

AU - Jensen, Allan

AU - Jimenez-Linan, Mercedes

AU - Joseph, Janine M.

AU - Karlan, Beth Y.

AU - Kaznowska, Ewa

AU - Kjaer, Susanne K.

AU - Kluz, Tomasz

AU - Koziak, Jennifer M.

AU - Lester, Jenny

AU - Longacre, Teri A.

AU - Lycke, Maria

AU - McGuire, Valerie

AU - Moysich, Kirsten B.

AU - Murphy, Rachel A.

AU - Orsulic, Sandra

AU - Ramus, Susan J.

AU - Rodríguez-Antona, Cristina

AU - Rothstein, Joseph H.

AU - Samra, Spinder

AU - Sieh, Weiva

AU - Steed, Helen

AU - Sundfeldt, Karin

AU - Talhouk, Aline

AU - Uciński, Jan

AU - Wang, Chen

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S.

AU - Wilkens, Lynne R.

AU - Songer, Thomas

AU - Brooks, Maria Mori

AU - Tang, Lu

AU - Modugno, Francesmary

PY - 2025/7

Y1 - 2025/7

N2 - 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.

AB - 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.

KW - Epithelial ovarian cancer

KW - Hormonal factors

KW - Hormone receptor

KW - Risk

KW - Survival

KW - androgen receptor

KW - estrogen receptor

KW - progesterone receptor

UR - https://www.scopus.com/pages/publications/105007159237

U2 - 10.1016/j.ygyno.2025.05.013

DO - 10.1016/j.ygyno.2025.05.013

M3 - Article

C2 - 40482607

AN - SCOPUS:105007159237

SN - 0090-8258

VL - 198

SP - 112

EP - 129

JO - Gynecologic Oncology

JF - Gynecologic Oncology

ER -

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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