title: Relationship of serum estrogens and metabolites with area and volume mammographic densities.
abstract: Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40-65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, gierachg@mail.nih.gov.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Berta M
authors.initials: BM
authors.lastname: Geller
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Vacek
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Chicoine
authors.forename: John A
authors.initials: JA
authors.lastname: Shepherd
authors.forename: Amir Pasha
authors.initials: AP
authors.lastname: Mahmoudzadeh
authors.forename: Jeff
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.forename: Sally D
authors.initials: SD
authors.lastname: Herschorn
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Timothy
authors.initials: T
authors.lastname: Veenstra
authors.forename: Barbara
authors.initials: B
authors.lastname: Fuhrman
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
mesh_terms: D000328:Adult; D000368:Aged; D000071060:Breast Density; D001943:Breast Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging*; D002853:Chromatography, Liquid; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008327:Mammography; D008875:Middle Aged; D011857:Radiographic Image Interpretation, Computer-Assisted; D053719:Tandem Mass Spectrometry
chemical_list: D004967:Estrogens