The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is a risk prediction model that is used to compute probabilities of carrying mutations in the high-risk breast and ovarian cancer susceptibility genes BRCA1 and BRCA2, and to estimate the future risks of developing breast or ovarian cancer.In this paper, we describe updates to the BOADICEA model that extend its capabilities, make it easier to use in a clinical setting and yield more accurate predictions.
BOADICEA has been validated in a large series of families from UK genetics clinics (Antoniou et al, 2008b).
In the United Kingdom, it is recommended as a risk assessment tool in the National Institute for Health and Care Excellence clinical guideline CG164 (National Institute for Health and Care Excellence, 2013) and has been incorporated in the guidelines of several countries for the management of familial breast cancer (Ontario Breast Screening Program, 2012; Riley et al, 2012; Smith et al, 2012).
To obtain risk predictions, BOADICEA considers the occurrence of breast, ovarian, pancreatic and prostate cancers in families (Antoniou et al, 2008a).
To provide a consistent model, the breast and ovarian cancer incidences over all assumed genetic effects are constrained to agree with population incidences (Antoniou et al, 2001).
The old implementation of the model assumes calendar period- and cohort-specific incidences for the United Kingdom that span the period 1960–1997, taken from the Cancer Incidence in Five Continents (CI5) publications (Ferlay et al, 2010).
These incidences were the most up-to-date and relevant cancer incidences available to us when the BOADICEA model was initially developed.However, breast, ovarian and prostate cancer incidences have increased over time (Hayat et al, 2007).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 andor 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.