K Tikk1, D Sookthai1, T Johnson1, S Rinaldi2, I Romieu2, A Tjønneland3, A Olsen3, K Overvad4, F Clavel-Chapelon5, L Baglietto6, H Boeing7, A Trichopoulou8, P Lagiou9, D Trichopoulos10, D Palli11, V Pala12, R Tumino13, S Rosso14, S Panico15, A Agudo16, V Menéndez17, M-J Sánchez18, P Amiano19, J M Huerta Castaño20, E Ardanaz21, H B Bueno-de-Mesquita22, E Monninkhof23, C Onland-Moret23, A Andersson24, M Sund25, E Weiderpass26, K-T Khaw27, T J Key28, R C Travis28, M J Gunter29, E Riboli29, L Dossus5, R Kaaks30. 1. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany. 2. Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. 3. Danish Cancer Society Research Center, Copenhagen. 4. Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. 5. INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women's Health Team, Villejuif; University of Paris Sud, UMRS, Villejuif; IGR, Villejuif, France. 6. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne; Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia. 7. Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany. 8. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens; Hellenic Health Foundation, Athens, Greece. 9. Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. 10. Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. 11. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy. 12. Epidemiology and Prevention Unit, National Tumor Institute (IRCCS), Milano. 13. Cancer Registry and Histopathology Unit, 'Civic-M. P. Arezzo' Hospital ASP, Ragusa. 14. Piedmont Cancer Registry, Centre for Epidemiology and Prevention in Oncology in Piedmont, Torino. 15. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. 16. Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, Barcelona. 17. Public Health Directorate, Asturias. 18. Granada Cancer Registry, Andalusian School of Public Health, Granada; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid. 19. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian. 20. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Department of Epidemiology, Murcia Regional Health Authority, Murcia. 21. Consortium for Biomedical Research in Epidemiology and Public Health (CIBER), Madrid; Navarre Public Health Institute, Pamplona, Spain. 22. National Institute for Public Health and the Environment (RIVM), Bilthoven; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College, London, UK. 23. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. 24. Department of Radiation Sciences, University of Umeå, Umeå. 25. Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. 26. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø; Department of Research, Cancer Registry of Norway, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Society of Public Health, Helsinki, Finland. 27. School of Clinical Medicine, University of Cambridge, Cambridge. 28. Cancer Epidemiology Unit, University of Oxford, Oxford, UK. 29. School of Public Health, Imperial College, London, UK. 30. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany. Electronic address: r.kaaks@dkfz.de.
Abstract
BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
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