Abstract
Abstract 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 a prospective cohort, the NYU Women's Health Study, was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls (1:2 matching) were included. Matching variables included age and date of blood donation, as well as phase and day of menstrual cycle. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured using direct radioimmunoassays. Free testosterone was calculated. Samples from a second blood donation at a median of 2 years after the first blood donation were also analyzed for 138 cases and 268 controls. Results: Premenopausal serum testosterone and free testosterone concentrations were positively associated with subsequent breast cancer risk. In models adjusted for known risk factors of breast cancer (BMI, age at menarche, family history of breast cancer, parity/age at first birth, and history of breast biopsy), the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9–2.3), 1.2 (95% CI, 0.7–1.9), 1.4 (95% CI, 0.9–2.3) and 1.8 (95% CI, 1.1–2.9) with the P value for trend of 0.04, and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7–1.8), 1.5 (95% CI, 0.9–2.3), 1.5 (95% CI, 0.9–2.3), and 1.8 (95% CI, 1.1–2.8) with a P value for trend of 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 (ICCs) for measurements of serial annual blood donations from the same individual were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls). Conclusions: Premenopausal concentrations of testosterone and free testosterone are positively associated with breast cancer risk. Results from other prospective studies are consistent with our results. Testosterone and free testosterone are also highly reliable (i.e. a single measurement is reflective of a woman's average level over time). Future studies should examine the contribution of including testosterone and free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A3.
Published Version
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