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
- Author(s)
- Fu, Z; Chudecka-Głaz, A; Borho, L; García, MJ; Taylor, SE; Høgdall, E; Kelemen, LE; Rodríguez-Antona, C; DeFazio, A; Uciński, J; 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; Cook, LS; Cybulski, C; Fasching, PA; Fereday, S; Fortner, RT; Goode, EL; Goodman, MT; Gronwald, J; Hartmann, A; Hernandez, BY; 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; Rothstein, JH; Samra, S; Sieh, W; Steed, H; Sundfeldt, K; Talhouk, A; Wang, C; Wentzensen, N; Whittemore, AS; Wilkens, LR; Songer, T; Brooks, MM; Tang, L; Modugno, F;
- Journal Title
- Gynecologic Oncology
- Publication Type
- Research article
- 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.
- Publisher
- Elsevier
- Keywords
- Humans; Female; *Ovarian Neoplasms/metabolism/mortality/pathology/epidemiology; *Receptors, Androgen/biosynthesis; *Receptors, Progesterone/biosynthesis; Middle Aged; Carcinoma, Ovarian Epithelial; *Estrogen Receptor alpha/biosynthesis; Aged; Risk Factors; *Receptors, Estrogen/biosynthesis; Adult; *Neoplasms, Glandular and Epithelial/metabolism/mortality/pathology; Obesity/epidemiology; Case-Control Studies; Epithelial ovarian cancer; Hormonal factors; Hormone receptor; Risk; Survival; androgen receptor; estrogen receptor; progesterone receptor
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1016/j.ygyno.2025.05.013
- Open Access at Publisher's Site
https://doi.org/10.1016/j.ygyno.2025.05.013- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-07-25 07:49:10
Last Modified: 2025-07-29 05:57:04