Founder BRCA1/2 mutations in the Europe #2 July 10, 2010Posted by ramunas in BRCA, breast cancer, cancer genetics, hereditary cancer, ovarian cancer.
Currently, in most countries clinical BRCA1/2 testing is offered after genetic counseling by clinical cancer geneticist (oncogeneticist) when mutation finding probability exceeds 10%, or even 20% (as in the UK) . Various selection criteria, based on family history, age at onset and tumors clinicopathological features, as well as computational risk prediction models (Claus, BRCAPRO, BOADICEA, IBIS, Myriad and Manchester scoring system [19, 20]) are used. Unfortunately, these models often underestimate the probability of finding a mutation, are validated only in some countries, are not particularly helpful for daily use and no consensus exist regarding their common use [9, 21]. Moreover, familial history is also absent or unknown in at least half of all mutation possitive families  and mutation detection methods varies between most centers.
It is now evident, that in a near future the uptake and demand for rapid BRCA1/2 mutations testing will increase and more flexible genetic counseling strategies will be needed. As new targeted therapies become available, more individuals will request testing to get access to specific treatments (i.e., PARP inhibitors), regardless of their a priori low risk and clinicians will force laboratories towards rapid testing results. This tendency is already seen in the centers enroling patients for PARP inhibitors clinical trials (van Osterweik, personal communication) as well as during peridiagnostic (presurgical) testing for a newly diagnozed breast cancer patients .
However, a full BRCA1 and BRCA2 gene screening still remains labor and time consuming challenge due to large genes size, diverse mutations or variants of unknown significance (VUS) and complexity of large genomic rearangements (LGRs), requiring special technical approach. This procedure still remains too complex and expensive to cover a broader target (e.g. all breast or ovarian cancer patients and their first degree relatives) and cannot be routinely applied in less privileged countries.
My full review article: Janavicius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control