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 BorosDavid 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^*

^*Corresponding author af dette arbejde

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.

Originalsprog	Engelsk
Tidsskrift	Gynecologic Oncology
Vol/bind	198
Sider (fra-til)	112-129
Antal sider	18
ISSN	0090-8258
DOI	https://doi.org/10.1016/j.ygyno.2025.05.013
Status	Udgivet - jul. 2025

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10.1016/j.ygyno.2025.05.013

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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

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, Zhuxuan; Borho, Lauren; Taylor, Sarah E et al.
I: Gynecologic Oncology, Bind 198, 07.2025, s. 112-129.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, bind 198, s. 112-129. https://doi.org/10.1016/j.ygyno.2025.05.013

@article{49553cc7f28245f29354b970c3924252,

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.",

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",

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.",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=105007159237&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2025.05.013

DO - 10.1016/j.ygyno.2025.05.013

M3 - Journal article

C2 - 40482607

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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