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J Natl Cancer Inst. 2015 May 8;107(7). pii: djv124. doi: 10.1093/jnci/djv124. Print 2015 Jul.

Practical problems with clinical guidelines for breast cancer prevention based on remaining lifetime risk.

Author information

1
: Joseph L. Mailman School of Public Health, Columbia University, New York, NY (ASQ, TS, MBT); Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany (ASQ, KS); Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany (ASQ, KS); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (ASW); Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Carlton, Victoria, Australia (JLH); Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea (JLH); Herbert Irving Comprehensive Cancer Center, Columbia Medical Center, New York, NY (MBT).
2
: Joseph L. Mailman School of Public Health, Columbia University, New York, NY (ASQ, TS, MBT); Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany (ASQ, KS); Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany (ASQ, KS); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (ASW); Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Carlton, Victoria, Australia (JLH); Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea (JLH); Herbert Irving Comprehensive Cancer Center, Columbia Medical Center, New York, NY (MBT). mt146@columbia.edu.

Abstract

BACKGROUND:

Clinical guidelines for breast cancer chemoprevention and MRI screening involve estimates of remaining lifetime risk (RLR); in the United States, women with an RLR of 20% or higher meet "high-risk" criteria for MRI screening.

METHODS:

We prospectively followed 1764 women without breast cancer to compare the RLRs and 10-year risks assigned by the risk models International Breast Cancer Intervention Study (IBIS) and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and to compare both sets of model-assigned 10-year risks to subsequent incidence of breast cancer in the cohort. We used chi-square statistics to assess calibration and the area under the receiver operating characteristic curve (AUC) to assess discrimination. All statistical tests are two-sided.

RESULTS:

The models classified different proportions of women as high-risk (IBIS = 59.3% vs BOADICEA = 20.1%) using the RLR threshold of 20%. The difference was smaller (IBIS = 52.9% vs BOADICEA = 43.2%) using a 10-year risk threshold of 3.34%. IBIS risks (mean = 4.9%) were better calibrated to observed breast cancer incidence (5.2%, 95% confidence interval (CI) = 4.2% to 6.4%) than were those of BOADICEA (mean = 3.7%) overall and within quartiles of model risk (P = .20 by IBIS and P = .07 by BOADICEA). Both models gave similar discrimination, with AUCs of 0.67 (95% CI = 0.61 to 0.73) using IBIS and 0.68 (95% CI = 0.62 to 0.74) using BOADICEA. Model sensitivities at thresholds for a 20% false-positive rate were also similar, with 41.8% using IBIS and 38.0% using BOADICEA.

CONCLUSION:

RLR-based guidelines for high-risk women are limited by discordance between commonly used risk models. Guidelines based on short-term risks would be more useful, as models are generally developed and validated under a short fixed time horizon (≤10 years).

PMID:
25956172
PMCID:
PMC4554256
DOI:
10.1093/jnci/djv124
[Indexed for MEDLINE]
Free PMC Article

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