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Evaluation of breast cancer risk assessment packages in the family history evaluation and screening programme

¹ University of Manchester, UK
² Academic Unit of Medical Genetics and Regional Genetics Service, St. Mary’s Hospital, Manchester, UK
³ Centre for Cancer Epidemiology, University of Manchester, UK
⁴ Department of Radiology, South Manchester University Hospital Trust, Manchester, UK
⁵ Department of Medical Oncology, Christie Hospital, Manchester, UK

Correspondence to:
Professor D G Evans
Academic Unit of Medical Genetics and Regional Genetics Service, St. Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK; gareth.evans{at}cmmc.nhs.uk]

Introduction: Accurate individualised breast cancer risk assessment is essential to provide risk–benefit analysis prior to initiating interventions designed to lower breast cancer risk. Several mathematical models for the estimation of individual breast cancer risk have been proposed. However, no single model integrates family history, hormonal factors, and benign breast disease in a comprehensive fashion. A new model by Tyrer and Cuzick has addressed these deficiencies. Therefore, this study has assessed the goodness of fit and discriminatory value of the Tyrer–Cuzick model against established models namely Gail, Claus, and Ford.

Methods: The goodness of fit and discriminatory accuracy of the models was assessed using data from 1933 women attending the Family History Evaluation and Screening Programme, of whom 52 developed cancer. All models were applied to these women over a mean follow up of 5.27 years to estimate risk of breast cancer.

Results: The ratios (95% confidence intervals) of expected to observed numbers of breast cancers were 0.48 (0.37 to 0.64) for Gail, 0.56 (0.43 to 0.75) for Claus, 0.49 (0.37 to 0.65) for Ford, and 0.81 (0.62 to 1.08) for Tyrer–Cuzick. The accuracy of the models for individual cases was evaluated using ROC curves. These showed that the area under the curve was 0.735 for Gail, 0.716 for Claus, 0.737 for Ford, and 0.762 for Tyrer–Cuzick.

Conclusion: The Tyrer–Cuzick model is the most consistently accurate model for prediction of breast cancer. The Gail, Claus, and Ford models all significantly underestimate risk, although the accuracy of the Claus model may be improved by adjustments for other risk factors.

Keywords: assessment; breast cancer; models; risk; validation

Abbreviations: ROC, receiver operating characteristic

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