Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics

Objectives: Genetic testing for the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 has important implications for the clinical management of people found to carry a mutation. However, genetic testing is expensive and may be associated with adverse psychosocial effects. To provide a cost-efficient and clinically appropriate genetic counselling service, genetic testing should be targeted at those individuals most likely to carry pathogenic mutations. Several algorithms that predict the likelihood of carrying a BRCA1 or a BRCA2 mutation are currently used in clinical practice to identify such individuals. Design: We evaluated the performance of the carrier prediction algorithms BOADICEA, BRCAPRO, IBIS, the Manchester scoring system and Myriad tables, using 1934 families seen in cancer genetics clinics in the UK in whom an index patient had been screened for BRCA1 and/or BRCA2 mutations. The models were evaluated for calibration, discrimination and accuracy of the predictions. Results: Of the five algorithms, only BOADICEA predicted the overall observed number of mutations detected accurately (ie, was well calibrated). BOADICEA also provided the best discrimination, being significantly better (p < 0.05) than all models except BRCAPRO ( area under the receiver operating characteristic curve statistics: BOADICEA=0.77, BRCAPRO=0.76, IBIS=0.74, Manchester=0.75, Myriad=0.72). All models under-predicted the number of BRCA1 and BRCA2 mutations in the low estimated risk category. Conclusions: Carrier prediction algorithms provide a rational basis for counselling individuals likely to carry BRCA1 or BRCA2 mutations. Their widespread use would improve equity of access and the cost-effectiveness of genetic testing

Medicine's Next Goldmine? The implications of new genetic health technologies for the health service

There is considerable uncertainty about the implications of the new genetics for health services. These are the enthusiasts who argue that molecular genetics will transform health care and others argue that the scope for genetic interventions is limited. The aim of this paper is to examine some of the questions, tensions and difficulties which face health care providers particularly in developed countries as they try to come to terms with the dilemmas raised by new genetic health care technologies (NGHTs). It identifies questions for research which may help the development of robust and flexible strategies for implementation