Abstract A8: Estrogen metabolism and mammographic density in postmenopausal women
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AbstractEstrogens play important roles in the pathophysiology of breast tumors and are recognized causal factors in the etiology of breast cancer. Parent estrogens (estrone and estradiol) can be hydroxylated at the 2, 4, or 16 position of the steroid ring, resulting in metabolites with different biological activity and availability. Estrogen metabolism shows great inter-individual variation, is modifiable, and may contribute to differences among women at risk of breast cancer. We conducted a cross-sectional study to investigate whether urinary estrogens and estrogen metabolites (jointly referred to as EM) are associated with mammographic density (MD), the strongest predictor of sporadic breast cancer risk among women apart from age.Methods: Postmenopausal women without breast cancer, aged 48–82 y, and reporting no current use of exogenous hormones were recruited and interviewed at a mammography clinic in Western NY in 2005. Concentrations of 15 EM were measured in first morning urine samples from 195 participants using liquid chromatography-tandem mass spectrometry. MD (%) was measured using computer-assisted analyses of digitized films. Linear models were used to assess associations of log-transformed EM concentrations and ratios with MD while adjusting for age, body mass index (BMI, kg/m2), and history of combination menopausal hormone therapy. We assessed effect modification by these factors and by years since menopause. Results: The median age of participants was 58, and median time since menopause was 8 years; 35% of participants were obese (BMI ≥30), and 33% had previously used combination menopausal hormones. Among all participants, urinary concentrations of parent estrogens were not associated with MD while some individual 2-pathway and 4-pathway EM had significant inverse associations with MD. Associations between EM profiles and MD were modified by years since menopause (≤8 or >8 y) and by obesity. Among women with a recent menopause, MD was positively associated with parent estrogens (p=0.02), and inversely associated with 2- and 4-hydroxylation pathway EM (p=0.03 and 0.02); these associations were not observed in women with a more distant menopause (pinteraction=0.02, 0.18, 0.16, respectively). Similarly, parent estrogens were directly associated with MD (p=0.003) among women who were obese but not among thinner counterparts (pinteraction=0.08).Conclusion: This is the first study to examine the relations between 15 EM and MD in postmenopausal women. EM profiles were most strongly associated with MD in subgroups with higher estrogen levels including obese women and those with a more recent menopause. In these groups, more extensive 2- and 4-hydroxylation of parent estrogens was associated with reduced MD. This pattern of metabolism may influence MD by facilitating clearance of estrogens from breast tissues.Citation Information: Cancer Prev Res 2011;4(10 Suppl):A8.
