title: Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study.
abstract: BACKGROUND
  Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug.
  
  
  METHODS
  We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided.
  
  
  RESULTS
  In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction.
  
  
  CONCLUSIONS
  The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. j.cuzick@qmul.ac.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: Stephen W
authors.initials: SW
authors.lastname: Duffy
authors.forename: Simon
authors.initials: S
authors.lastname: Cawthorn
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: John F
authors.initials: JF
authors.lastname: Forbes
authors.forename: Ruth M L
authors.initials: RM
authors.lastname: Warren
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D044362:Australasia; D001940:Breast / Q000187:drug effects* / Q000473:pathology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D006801:Humans; D016015:Logistic Models; D008327:Mammography; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D006113:United Kingdom
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen