BRCA1, BRCA2 and breast cancer: a concise clinical review

Less than 5% of breast cancers are hereditary, but over 90% of hereditary breast cancers are caused by a mutation of either BRCA1 or BRCA2. The mutation may be inherited from either the maternal or the paternal side of the family. Clinicians should consider specific criteria in the family history to determine when a patient may benefit from counselling and appropriate testing. Testing is generally offered only to patients who are at high risk and is currently estimated to have a sensitivity of about 85%. Test protocols are primarily oriented to detecting frameshift and nonsense mutations that cause premature protein truncations. Missense mutations also occur, but they are less common and sometimes not clearly of clinical significance. Laboratory results need to be correlated with the clinical picture, and genetic counselling is a critical component in maximizing the benefits of testing. In the future, application of more refined clinical criteria, as well as expected improvements in laboratory techniques, will undoubtedly lead to significantly better outcomes and options in surveillance and management for hereditary breast and ovarian cancer syndromes caused by mutations of BRCA1 and BRCA2.