Email updates

Keep up to date with the latest news and content from Breast Cancer Research and BioMed Central.

Open Access Highly Accessed Research article

Breast cancer risk assessment across the risk continuum: genetic and nongenetic risk factors contributing to differential model performance

Anne S Quante123, Alice S Whittemore4, Tom Shriver1, Konstantin Strauch23 and Mary B Terry15*

Author Affiliations

1 Department of Epidemiology, Columbia University, 722 West 168th Street 724A, New York, NY 10032, USA

2 Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany

3 Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, 85764 Neuherberg, Germany

4 Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA

5 Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, 701 West 168th Street, New York, NY 10032, USA

For all author emails, please log on.

Breast Cancer Research 2012, 14:R144  doi:10.1186/bcr3352

Published: 5 November 2012

Abstract

Introduction

Clinicians use different breast cancer risk models for patients considered at average and above-average risk, based largely on their family histories and genetic factors. We used longitudinal cohort data from women whose breast cancer risks span the full spectrum to determine the genetic and nongenetic covariates that differentiate the performance of two commonly used models that include nongenetic factors - BCRAT, also called Gail model, generally used for patients with average risk and IBIS, also called Tyrer Cuzick model, generally used for patients with above-average risk.

Methods

We evaluated the performance of the BCRAT and IBIS models as currently applied in clinical settings for 10-year absolute risk of breast cancer, using prospective data from 1,857 women over a mean follow-up length of 8.1 years, of whom 83 developed cancer. This cohort spans the continuum of breast cancer risk, with some subjects at lower than average population risk. Therefore, the wide variation in individual risk makes it an interesting population to examine model performance across subgroups of women. For model calibration, we divided the cohort into quartiles of model-assigned risk and compared differences between assigned and observed risks using the Hosmer-Lemeshow (HL) chi-squared statistic. For model discrimination, we computed the area under the receiver operator curve (AUC) and the case risk percentiles (CRPs).

Results

The 10-year risks assigned by BCRAT and IBIS differed (range of difference 0.001 to 79.5). The mean BCRAT- and IBIS-assigned risks of 3.18% and 5.49%, respectively, were lower than the cohort's 10-year cumulative probability of developing breast cancer (6.25%; 95% confidence interval (CI) = 5.0 to 7.8%). Agreement between assigned and observed risks was better for IBIS (HL X42 = 7.2, P value 0.13) than BCRAT (HL X42 = 22.0, P value <0.001). The IBIS model also showed better discrimination (AUC = 69.5%, CI = 63.8% to 75.2%) than did the BCRAT model (AUC = 63.2%, CI = 57.6% to 68.9%). In almost all covariate-specific subgroups, BCRAT mean risks were significantly lower than the observed risks, while IBIS risks showed generally good agreement with observed risks, even in the subgroups of women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative).

Conclusions

Models developed using extended family history and genetic data, such as the IBIS model, also perform well in women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative). Extending such models to include additional nongenetic information may improve performance in women across the breast cancer risk continuum.