© 2005 Oxford University Press
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Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk Within the European Prospective Investigation into Cancer and Nutrition (EPIC)
Affiliations of authors: International Agency for Research on Cancer (IARC-WHO), Lyon, France (RK, SR, LD, CB, TN, PF, NS, ER), Epidemiology Unit, Cancer Research UK, University of Oxford, Oxford, UK (TK, AR), National Cancer Institute, Milan, Italy (FB, GS, VK), Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, Netherlands (PP, CHvG, NCO-M), MRC Dunn Human Nutrition Unit, Welcome Trust/MRC Building, Cambridge, UK (SB), Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK (KTK), Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, Netherlands (HBBdM), German Institute of Human Nutrition, Department of Epidemiology, Potsdam-Rehbrücke, Germany (HB, PHL), Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany (JCC, GN), INSERM, Institut Gustave Roussy, Villejuif, France (FCC, AF, A. Thiebaut), Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain (CAG), The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark (A.Tjønneland, AO), Department of Epidemiology and Social Medicine, Aarhus University, Aarhus, Denmark (KO), Sección Información Sanitaria, Consejería de Salud y Servicios Sanitarios de Asturias, Asturias, Spain (JRQ), Epidemiology Department, Murcia Health Council, Murcia, Spain (MDC), Public Health Institute of Navarra, Spain (ABG), Public Health Division of Gipuzkoa, Health Department of the Basque Country, Donostia-San Sebastian. Spain (PA), Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy (DP), Department for Clinical and Experimental Medicine, Federico II University Naples, Italy (SP), Cancer Registry, Azienda Ospedaliera "Civile M.P. Arezzo," Ragusa, Italy (RT); Imperial College London, UK and University of Torino, Italy (PV); University of Athens Medical School, Athens, Greece (EC, A. Trichopoulou, DT)
Correspondence to: Dr. Rudolf Kaaks, Nutrition and Hormones Group, International Agency for Research on Cancer (IARC-WHO), 150 cours Albert-Thomas, 69372 Lyon cedex 08, France (e-mail: kaaks{at}iarc.fr).
Background: Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk. Methods: Levels of DHEAS, (
4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided. Results: Increased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; Ptrend = .01), androstenedione (OR for highest versus lowest quartile = 1.56, 95% CI = 1.05 to 2.32; Ptrend = .01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; Ptrend = .10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; Ptrend = .06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels of the other hormones. Conclusions: Our results support the hypothesis that elevated blood concentrations of androgens are associated with an increased risk of breast cancer in premenopausal women.
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