• Rudolf Kaaks, Kaja Tikk, Disorn Sookthai, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Françoise Clavel-Chapelon, Laure Dossus, Laura Baglietto, Sabina Rinaldi, Veronique Chajes, Isabelle Romieu, Heiner Boeing, Madlen Schütze, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Sabina Sieri, Rosario Tumino, Fulvio Ricceri, Amalia Mattiello, Genevieve Buckland, Jose Ramón Quirós, María-José Sánchez, Pilar Amiano, Maria-Dolores Chirlaque, Aurelio Barricarte, Bas Bueno-de-Mesquita H H, Carla H van Gils, Petra H Peeters, Anne Andersson, Malin Sund, Elisabete Weiderpass, Kay-Tee Khaw, Nick Wareham, Timothy J Key, Ruth C Travis, Melissa A Merritt, Marc J Gunter, Elio Riboli, and Annekatrin Lukanova.
• Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
• Int. J. Cancer. 2014 Apr 15; 134 (8): 1947-57.

AbstractResults from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1  = 1.56 (95% CI 1.15-2.13), ptrend  = 0.02 for testosterone and ORQ4-Q1  = 1.33 (95% CI 0.99-1.79), ptrend  = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1  = 1.32 (95% CI 0.87-2.01), ptrend  = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1  = 0.94 (95% CI 0.60-1.47), ptrend  = 0.34, phet  = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen. © 2013 UICC.

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