There are several risk assessment tools available to help decide whether a woman carries an increased risk of breast cancer and these have been developed by Clinical Genetics units. If a patient has been classified as having a moderately increased risk of breast cancer then it is advised that she have annual mammography between the ages of 40 and 50. If she has been designated high-risk then there is a possibility that her family harbours a mutation in one of the known high-risk genes BRCA 1 or 2. Any woman with a greater than 20-25% lifetime risk of breast cancer (including women who have had mantle radiotherapy for lymphoma) should consider enhanced surveillance or risk-reducing surgery. MRI breast screening provides enhanced surveillance and this aims to pick up breast cancers at an early/ treatable stage. Risk-reducing mastectomies and immediate reconstructions will reduce a BRCA gene carrier’s lifetime breast cancer risk to around 2-4%. A trained Consultant Breast Surgeon or a Specialist Nurse will be able to perform a risk-assessment for any individual who is worried about their risk of breast cancer based on their family history.

The products of the BRCA genes are thought to participate in the monitoring and/ or repair of DNA damage. If their function is impaired, DNA damage can build up which ultimately leads to cancer. The BRCA 1 and 2 genes are large and sited on the long arms of chromosomes 17 and 13 respectively. They are inherited in an autosomal dominant fashion, which means that 50% of the children of a woman (or man) who carry mutated BRCA 1 or 2 genes will also inherit the faulty gene. Some ethnic groups, such as Ashkenazi Jews have persistent mutations in BRCA 1 and BRCA 2 and 2% of their population carry these mutations. For those women who are found to have a BRCA-1 or BRCA-2 mutation, their lifetime risk of breast cancer (to the age 70) is approximately 70% for BRCA-1 carriers and 55% for BRCA-2 carriers. There is also around a 40% lifetime risk of ovarian cancer. However, nearly 15% of all BRCA1/2 mutation tests find variants of unknown significance (VUS) and it is thought that approximately 10% of VUS are pathological ie. increase the risk of breast and ovarian cancer. There are some methods available to determine whether a variant is likely to convey a significant future risk of breast cancer but these are not always predictive. Therefore, finding a VUS can be very stressful for a family as the uncertainty can provoke severe anxiety. Genetic laboratories are advised to maintain a database of all VUS because it is hoped that as information accumulates, the future breast/ ovarian cancer risk for affected families will become clearer.

Testing for a BRCA gene mutation can be problematic for individuals with a high risk of breast cancer. The genes are very large and there are hundreds of potential mutations some with uncertain significance. Tests for a gene mutation should ideally be carried out first on an affected family member ie. someone who has already had breast cancer. This is called mutation searching or screening and it aims to find the gene mutation specific to that family. A search for a BRCA gene mutation should aim to be as sensitive as possible and it is suggested that the whole genes should be scanned. Before having the test, a person should be counselled about the probability of finding the mutation and the implications for the individual and the rest of their family if a mutation is found. It is also important that the individual understands the meaning of a negative result or a variant of unknown significance. It is recommended that BRCA 1/2 genetic testing be offered to unaffected individuals or patients newly diagnosed with breast/ ovarian cancer if their combined probability of a BRCA 1/2 mutation is 10% or more.

Male breast cancer is a very rare disease. It is thought that men who carry the BRCA-2 gene mutation have a lifetime risk of breast cancer (to the age of 70) of approximately 7%. Because there are so few cases of breast cancer in men it is difficult to quantify the lifetime risk for men with a BRCA-1 gene mutation. Men with BRCA 1/2-gene mutations also have a higher risk of developing prostate cancer. The risk of prostate cancer in BRCA-2 mutation carriers may increase as much as 9 fold in those under the age of 65. Therefore, a man with a strong history of breast and ovarian cancer in his female relatives may be a potential BRCA1/ 2 gene mutation carrier.