Circulating serum xenoestrogens and mammographic breast density

INTRODUCTION: Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk). METHODS: We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method. RESULTS: Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P(trend )= 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P(trend )= 0.07). No other chemicals demonstrated associations with percentage breast density. CONCLUSIONS: Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.