Research article
Premenopausal serum androgens and breast cancer risk: a nested case-control study
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* Corresponding author: Anne Zeleniuch-Jacquotte anne.jacquotte@nyumc.org
1 Department of Environmental Medicine, New York University School of Medicine, 650 First Avenue, New York, NY 10016, USA
2 New York University Cancer Institute, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA
3 Division of Cancer Epidemiology, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
4 International Agency for Research on Cancer, 150, Cours Albert Thomas, 69372 Lyon Cedex 08, France
5 Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
6 Unit of Cancer Epidemiology, Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Biopôle 1, 2 Route de la Corniche, CH-1066 Epalinges, Switzerland
7 Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima, 732-0815, Japan
Breast Cancer Research 2012, 14:R32 doi:10.1186/bcr3117
Published: 16 February 2012Abstract
Introduction
Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.
Methods
A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.
Results
Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls).
Conclusions
Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.