title: Relationship of Terminal Duct Lobular Unit Involution of the Breast with Area and Volume Mammographic Densities.
abstract: Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLU), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (perilesional). Three measures inversely related to TDLU involution (TDLU count/mm(2), median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40-65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent perilesional MD (P trend = 0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P trend<0.05) and absolute perilesional MD (P = 0.003). Acini count was directly associated with absolute perilesional MD (P = 0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P trend ≤ 0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in perilesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction.
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. gierachg@mail.nih.gov.
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Gierach
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Deesha A
authors.initials: DA
authors.lastname: Patel
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Laura
authors.initials: L
authors.lastname: Linville
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daphne
authors.initials: D
authors.lastname: Papathomas
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johnson
authors.affiliation: University of Vermont, Burlington, Vermont.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Chicoine
authors.affiliation: University of Vermont, Burlington, Vermont.
authors.forename: Sally D
authors.initials: SD
authors.lastname: Herschorn
authors.affiliation: University of California, San Francisco, San Francisco, California.
authors.forename: John A
authors.initials: JA
authors.lastname: Shepherd
authors.affiliation: University of California, San Francisco, San Francisco, California.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wang
authors.affiliation: University of California, San Francisco, San Francisco, California.
authors.forename: Serghei
authors.initials: S
authors.lastname: Malkov
authors.affiliation: University of Vermont, Burlington, Vermont.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Vacek
authors.affiliation: University of Vermont, Burlington, Vermont.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Weaver
authors.affiliation: University of California, San Francisco, San Francisco, California.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.affiliation: University of California, San Francisco, San Francisco, California.
authors.forename: Amir Pasha
authors.initials: AP
authors.lastname: Mahmoudzadeh
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maya
authors.initials: M
authors.lastname: Palakal
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jackie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hannah
authors.initials: H
authors.lastname: Oh
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hisani N
authors.initials: HN
authors.lastname: Horne
authors.affiliation: University of Vermont, Burlington, Vermont.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Sprague
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Breast and Gynecologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001940:Breast / Q000473:pathology*; D000071060:Breast Density; D001943:Breast Neoplasms / Q000150:complications / Q000209:etiology* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000473:pathology; D008327:Mammography; D008875:Middle Aged; D009367:Neoplasm Staging; D017697:Premenopause; D011379:Prognosis; D012307:Risk Factors; D047368:Tumor Burden