title: Mammographic breast density refines Tyrer-Cuzick estimates of breast cancer risk in high-risk women: findings from the placebo arm of the International Breast Cancer Intervention Study I.
abstract: BACKGROUND
  Mammographic density is well-established as a risk factor for breast cancer, however, adjustment for age and body mass index (BMI) is vital to its clinical interpretation when assessing individual risk. In this paper we develop a model to adjust mammographic density for age and BMI and show how this adjusted mammographic density measure might be used with existing risk prediction models to identify high-risk women more precisely.
  
  
  METHODS
  We explored the association between age, BMI, visually assessed percent dense area and breast cancer risk in a nested case-control study of women from the placebo arm of the International Breast Cancer Intervention Study I (72 cases, 486 controls). Linear regression was used to adjust mammographic density for age and BMI. This adjusted measure was evaluated in a multivariable logistic regression model that included the Tyrer-Cuzick (TC) risk score, which is based on classical breast cancer risk factors.
  
  
  RESULTS
  Percent dense area adjusted for age and BMI (the density residual) was a stronger measure of breast cancer risk than unadjusted percent dense area (odds ratio per standard deviation 1.55 versus 1.38; area under the curve (AUC) 0.62 versus 0.59). Furthermore, in this population at increased risk of breast cancer, the density residual added information beyond that obtained from the TC model alone, with the AUC for the model containing both TC risk and density residual being 0.62 compared to 0.51 for the model containing TC risk alone (P =0.002).
  
  
  CONCLUSIONS
  In women at high risk of breast cancer, adjusting percent mammographic density for age and BMI provides additional predictive information to the TC risk score, which already incorporates BMI, age, family history and other classic breast cancer risk factors. Furthermore, simple selection criteria can be developed using mammographic density, age and BMI to identify women at increased risk in a clinical setting.
  
  
  BACKGROUND
  http://www.controlled-trials.com/ISRCTN91879928 (Registered: 1 June 2006).
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.forename: Hanna
authors.initials: H
authors.lastname: Birke
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stone
authors.forename: Ruth M L
authors.initials: RM
authors.lastname: Warren
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pinney
authors.forename: Adam R
authors.initials: AR
authors.lastname: Brentnall
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Duffy
authors.forename: Anthony
authors.initials: A
authors.lastname: Howell
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000071060:Breast Density; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities* / Q000473:pathology; D008327:Mammography; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010919:Placebos; D013629:Tamoxifen