Tyrercuzick International Breast Cancer Intervention Study

This is the most recently developed of the breast cancer risk assessment models (32). It was developed using published data regarding BRCA1 and BRCA2 mutation carrier frequencies from a study of mother-daughter pairs (33) and penetrance estimates from the Breast Cancer Linkage Consortium (34) rather than one specific dataset. There are two parts to the model's calculations: a "genetic" part and a "personal risk factors" part. Like the BRCAPRO model, International Breast Cancer Intervention Study (IBIS) uses Bayesian calculations as a basis for the genetic part of the model. The Bayesian variables used are BRCA1 mutation, BRCA2 mutation, and "other genetic risk factor," an as yet unknown low-penetrance gene that is assumed to follow an autosomal-dominant inheritance pattern. Like BOADICEA, IBIS can incorporate exact family relationships and is not restricted to a certain number of first- and second-degree relatives in order to make its assessment. It is also capable of dealing with bilateral breast cancer but only in first-degree relatives of the proband. The cancers considered, however, are only breast and ovarian, like many of the other models previously discussed in this chapter.

Uniquely, at present, however, IBIS incorporates personal risk factors into its calculation. A number of risk factors have long been known to influence an individual's risk of breast and ovarian cancer in the general population. These are primarily related to hormonal and reproductive factors. Research is currently under way via the EMBRACE study to ascertain whether these known risk factors also influence the likelihood of breast and/or ovarian cancer developing in BRCA1/2 mutation carriers.

The personal risk factors incorporated into the IBIS model are the ages at menarche, first childbirth and menopause, parity, height, and body mass index, and two diagnoses associated with increased risk, namely atypical hyperplasia and lobular carcinoma in situ. Both these diagnoses are known to be associated with at least a fourfold increase in risk in the general population (35,36). Some risk factors have not yet been included. These are the administration of exogenous hormones such as the oral contraceptive pill and hormone replacement therapy and the presence of ductal carcinoma in situ.

In using the model, the genetic risks are calculated first, and then the personal risk factors are used to modify the genetic risk to create a personal calculation for the individual. Calculations of the likelihood of carrying a BRCA1/2 mutation and of developing breast or ovarian cancer are possible.

IBIS is such a new risk assessment model that it has not yet been comprehensively validated. In one study of prediction of cancer risks, involving 3170 women in the United Kingdom, IBIS outperformed other models such as BRCAPRO and Claus (24). Like many of the other models available, IBIS is computer based. It remains to be seen whether it is user friendly in the clinical setting.

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