title: Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk.
abstract: Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown.
  
  
  
  We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate.
  
  
  
  Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51).
  
  
  
  We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Byrne
authors.affiliation: Cancer Registry of Norway, Institute of Population Based Cancer Research, Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Martin
authors.affiliation: The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Peck
authors.affiliation: Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
authors.forename: Elodia B
authors.initials: EB
authors.lastname: Cole
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Donglin
authors.initials: D
authors.lastname: Zeng
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.affiliation: Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Yaffe
authors.affiliation: Ontario Cancer Institute, Toronto, Ontario, Canada.
authors.forename: Norman F
authors.initials: NF
authors.lastname: Boyd
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Stony Brook School of Medicine, Stony Brook, NY, USA.
authors.forename: Dorothy S
authors.initials: DS
authors.lastname: Lane
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, USA.
authors.forename: Etta D
authors.initials: ED
authors.lastname: Pisano
mesh_terms: D000368:Aged; D000071060:Breast Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D016015:Logistic Models; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate