title: Tamoxifen and breast density in women at increased risk of breast cancer.
abstract: BACKGROUND
  Although mammographic breast density is associated with the risk of breast cancer and is influenced by hormone levels, the effects of tamoxifen on breast density in healthy women and whether tamoxifen-induced density changes are associated with breast cancer risk are unclear. We investigated mammographic breast density in healthy women with an increased risk of breast cancer at baseline and during 54 months of tamoxifen treatment.
  
  
  METHODS
  Mammograms were reviewed from 818 breast cancer-free women (388 in the tamoxifen group and 430 in the placebo group) at high risk for breast cancer, from the International Breast Cancer Intervention Study I, a trial of tamoxifen for breast cancer prevention. Breast density measurements, at baseline and during treatment, were obtained at 12- to 18-month intervals. Multivariable analysis was used to assess associations with breast density. All statistical tests were two-sided.
  
  
  RESULTS
  Breast density at baseline was similar in placebo (42.6%, 95% confidence interval [CI] = 39.6% to 45.6%) and tamoxifen (41.9%, 95% CI = 38.8% to 45.0%) groups. The main determinants of breast density at baseline were age, menopausal status, body mass index, and previous atypical hyperplasia. A greater density reduction in the tamoxifen group (7.9%, 95% CI = 6.9% to 8.9%) than in the placebo group (3.5%, 95% CI = 2.7% to 4.3%) was apparent within 18 months of treatment (P<.001); the reduction in density continued until 54 months of treatment. After 54 months of tamoxifen treatment, breast density was 28.2% (decrease from baseline = 13.7%, 95% CI = 12.3% to 15.1%; P<.001) in the tamoxifen group and 35.3% (decrease from baseline = 7.3%, 95% CI = 6.1% to 8.4%; P<.001) in the placebo group. The tamoxifen-associated density reduction was apparent in all subgroups, but there was a statistically significant interaction with age. In women aged 45 years or younger at entry, the net reduction with tamoxifen was 13.4% (95% CI = 8.6% to 18.1%), whereas in women older than 55 years, it was 1.1% (95% CI = -3.0% to 5.1%).
  
  
  CONCLUSIONS
  Tamoxifen treatment was associated with reduction in breast density, most of which occurred during the first 18 months of treatment.
authors.affiliation: Cancer Research UK, Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary College, University of London, London, UK. jack.cuzick@cancer.org.uk
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pinney
authors.forename: Ruth M L
authors.initials: RM
authors.lastname: Warren
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Duffy
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001940:Breast / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000517:prevention & control*; D004311:Double-Blind Method; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008327:Mammography; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen