Risk categorisation: near population, moderate-risk and high-risk groups of breast and ovarian cancer
As already mentioned, familial risk of breast and ovarian cancer can be seen to occur along a continuum. The greater the number of affected relatives who are closely related to the proband, and the younger they are at the time of diagnosis, the higher the level of inherited risk. For the purpose of genetic assessment, family histories are placed into one of three risk categories which are ‘near population risk’, ‘moderate risk’ and ‘high risk’. This concept of a cancer risk continuum is illustrated in Fig. 14.1 through the use of the risk categories and a risk assessment model called the Manchester score (Table 14.1). With a progressive increase in the strength of family history, the risk category also increases, as does the likelihood of there being a single gene mutation.
The National Institute for Health and Care Excellence (NICE) guidance (NICE, 2013) suggests using either a manual model such as the Manchester scoring system or a computer-based model like BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) (Antoniou et al., 2004, 2008) to assess the inherited risk of breast cancer.
The Manchester score was devised by Evans et al. in 2004 to provide a robust, easy to use and quick method of calculating the probability of detecting a BRCA1/2 mutation in a family with a cancer family history. It does not, however, estimate an individual’s probability of being a carrier. In 2009 it was updated with histopathological information to reflect advances in the understanding of BRCA-related tumour characteristics such as tumour type and hormone receptor status (Evans et al., 2009). Scores are assigned based on the tumour type and age of the affected individual. A score of 15 equates to a 10% likelihood of detecting a BRCA mutation and is the current threshold for offering genetic testing according to NICE guidelines (NICE, 2013). It does not take into account rare BRCA-re- lated cancers or special cases where BRCA founder mutations may be prevalent in specific populations. Application of the Manchester score is illustrated by the use of adapted family histories (see Figs 14.3 and 14.4).
BOADICEA also estimates the likelihood of carrying a BRCA1/2 mutation but in an individual, and is therefore dependent on the sensitivity of the testing method used. It requires access to a computer and can be time-consuming to perform during a clinical consultation. In contrast to the Manchester score, it does incorporate information regarding Ashkenazi Jewish ancestry as well as the results of any BRCA1/2 testing that has already been performed in the family. Non-genetic factors, however, are currently not taken into account in the BOADICEA model. A paper validating the performance of both these models and others reported that BOADICEA is well calibrated and has a superior discriminatory power to most other models for detecting families likely to harbour BRCA mutations (Antoniou et al., 2008).
Secondary-care providers can use methods that calculate carrier probability, such as BOADICEA or the Manchester scoring system, to help determine eligibility for referral to specialist genetic services and genetic testing thresholds (NICE, 2013).
Figure 14.1 Continuum of breast and ovarian cancer risk.