Predicting risk of breast cancer in postmenopausal women by hormone receptor status

J Natl Cancer Inst. 2007 Nov 21;99(22):1695-705. doi: 10.1093/jnci/djm224. Epub 2007 Nov 13.


Background: Strategies for estrogen receptor (ER)-positive breast cancer risk reduction in postmenopausal women require screening of large populations to identify those with potential benefit. We evaluated and attempted to improve the performance of the Breast Cancer Risk Assessment Tool (i.e., the Gail model) for estimating invasive breast cancer risk by receptor status in postmenopausal women.

Methods: In The Women's Health Initiative cohort, breast cancer risk estimates from the Gail model and models incorporating additional or fewer risk factors and 5-year incidence of ER-positive and ER-negative invasive breast cancers were determined and compared by use of receiver operating characteristics and area under the curve (AUC) statistics. All statistical tests were two-sided.

Results: Among 147,916 eligible women, 3236 were diagnosed with invasive breast cancer. The overall AUC for the Gail model was 0.58 (95% confidence interval [CI]=0.56 to 0.60). The Gail model underestimated 5-year invasive breast cancer incidence by approximately 20% (P<.001), mostly among those with a low estimated risk. Discriminatory performance was better for the risk of ER-positive cancer (AUC = 0.60, 95% CI = 0.58 to 0.62) than for the risk of ER-negative cancer (AUC = 0.50, 95% CI = 0.45 to 0.54). Age and age at menopause were statistically significantly associated with ER-positive but not ER-negative cancers (P=.05 and P=.04 for heterogeneity, respectively). For ER-positive cancers, no additional risk factors substantially improved the Gail model prediction. However, a simpler model that included only age, breast cancer in first-degree relatives, and previous breast biopsy examination performed similarly for ER-positive breast cancer prediction (AUC=0.58, 95% CI= 0.56 to 0.60); postmenopausal women who were 55 years or older with either a previous breast biopsy examination or a family history of breast cancer had a 5-year breast cancer risk of 1.8% or higher.

Conclusions: In postmenopausal women, the Gail model identified populations at increased risk for ER-positive but not ER-negative breast cancers. A model with fewer variables appears to provide a simpler approach for screening for breast cancer risk.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alcohol Drinking / adverse effects
  • Area Under Curve
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Body Weight
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / etiology
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / epidemiology
  • Confounding Factors, Epidemiologic
  • Ethnicity / statistics & numerical data
  • Female
  • Humans
  • Logistic Models
  • Middle Aged
  • Models, Statistical
  • Motor Activity
  • Multivariate Analysis
  • Odds Ratio
  • Postmenopause*
  • Predictive Value of Tests
  • ROC Curve
  • Receptors, Estrogen / analysis*
  • Reproductive History
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects
  • Surveys and Questionnaires
  • United States / epidemiology
  • Women's Health


  • Biomarkers, Tumor
  • Receptors, Estrogen