Phenol Xenoestrogens and Mammographic Breast Density

Abstract

Abstract Concerns have been raised, largely on the basis of laboratory studies, regarding exposure to phenols, particularly bisphenol-A (BPA), in relation to hormone-related cancers. BPA is present in plastic consumer products including canned food linings and #7 polycarbonate plastics. According to recent NHANES data, human exposure as measured in urine is widespread (about 93% of people aged >5) and more common in females than males (Calafat EHP 2008). Concern regarding BPA in relation to breast cancer risk is based on in vivo and in vitro studies that suggest BPA may have a role in estrogen metabolism and mammary gland development. We examined the cross-sectional association of circulating serum levels of 3 phenols with mammographic breast density - a strong marker for breast cancer risk. A total of 264 postmenopausal women ages 55–70 years with no history of postmenopausal hormone use were recruited from mammography clinics in Madison, Wisconsin. Subjects completed a questionnaire regarding known breast cancer risk factors and provided a blood sample that was analyzed for octylphenol, nonylphenol, and BPA. Percent breast density (mean 15.3%, range 0.4–71.2%) was measured from subjects' mammograms using a computer-assisted thresholding method (Cumulus software). Since phenol levels are higher in the urine than in the serum, as expected many women had undetectable levels of the phenols in their serum: 86.7% octylphenol, 58.7% nonylphenol, and 73.1% BPA. After adjusting for age and body mass index in analysis of variance models, women with detectable serum BPA levels above the median (>0.56 ng/mL; N = 35) had higher percent breast density than women with BPA levels below the median (0.01–0.56 ng/mL; N = 36) and women with no detectable BPA (N = 193) in their serum (17.8% vs. 13.3% vs 12.7%, respectively; P = 0.01). Breast density was not associated with serum levels of either octylphenol or nonylphenol (P = 0.77, P = 0.36, respectively). Given that this study suggests that higher levels of BPA were associated with a clinically-relevant 5% greater breast density, further investigation into the potential influence of BPA on breast cancer risk using human populations is warranted. Supported by DOD BC062649, Komen FAS0703857, and NIH R03 CA139548.