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.
- Authors:
- Z Fu, L Borho, SE Taylor, LE Kelemen, A DeFazio, PM Webb, M Köbel, NS Meagher, R Na, AC Antoniou, AH Brand, CJ Kennedy, N Nevins, PDP Pharoah, YB Shvetsov, SJ Winham, J Alsop, MW Beckmann, A Bolithon, J Boros, DDL Bowtell, JD Brenton, ME Carney, A Chudecka-Głaz, LS Cook, C Cybulski, PA Fasching, S Fereday, RT Fortner, MJ García, EL Goode, MT Goodman, J Gronwald, A Hartmann, BY Hernandez, E Høgdall, DG Huntsman, A Jensen, M Jimenez-Linan, JM Joseph, BY Karlan, E Kaznowska, SK Kjaer, T Kluz, JM Koziak, J Lester, TA Longacre, M Lycke, V McGuire, KB Moysich, RA Murphy, S Orsulic, SJ Ramus, C Rodríguez-Antona, JH Rothstein, S Samra, W Sieh, H Steed, K Sundfeldt, A Talhouk, J Uciński, C Wang, N Wentzensen, AS Whittemore, LR Wilkens, T Songer, MM Brooks, L Tang, F Modugno
- Journal:
- Gynecol Oncol
- Citation info:
- 198:112-129
- Publication date:
- 1st Jul 2025
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- DOI