BOADICEA (Antoniou et al. 2004, 2008; Lee et al. 2014) is a risk prediction model for familial breast and ovarian cancer. The model is used to compute BRCA1 and BRCA2 mutation carrier probabilities and age-specific risks of breast and ovarian cancer. It was developed using complex segregation analysis of breast and ovarian cancer based on a combination of families identified through population-based studies of breast cancer, and families with multiple affected individuals who had been screened for BRCA1 and BRCA2 mutations. The latest version of the model was based on 2785 families, of which 537 segregated BRCA1 and/or BRCA2 mutations. BOADICEA models the simultaneous effects of BRCA1 and BRCA2 mutations and assumes that the residual familial clustering of breast cancer is explained by a polygenic component (a large number of genes each of small effect on risk) with a variance that decreases linearly with age. BOADICEA is implemented in the pedigree analysis software MENDEL and can be used on families of an arbitrary size and structure. The model can incorporate mutation screening data in any combination of individuals and allows for the effects of reduced sensitivity of the BRCA1 and BRCA2 mutation testing techniques.
Model validation and use in clinical guidelines
BOADICEA has been validated in a large series of families from UK genetics clinics (Antoniou et al. 2008). MacGinnis et al. (2013) also described the performance of BOADICEA for breast cancer risk prediction. In the United Kingdom, it is recommended as a risk assessment tool in the National Institute for Health and Care Excellence clinical guideline CG164 and has been incorporated in the guidelines of several countries for the management of familial breast cancer (e.g. Riley et al. 2012; Smith et al. 2012).
Scientific innovation
BOADICEA is an example of scientific innovation. BOADICEA was the world’s first polygenic breast cancer risk model, and it remains the only one available to the global healthcare community. It was also the first breast cancer risk model to incorporate pathology data and population-specific cancer incidences in risk calculations. Similarly, the BOADICEA Web Application was the first breast cancer risk model interface to: (1) be implemented on the Web, (2) include pedigree building for families of arbitrary size and structure beyond 2nd degree, (3) check that all family members within an uploaded pedigree are genealogically connected to the index, (4) include Web-based batch processing, and (5) generate processing report PDFs.