It is important to remember that the vast majority of breast cancer in the UK is sporadic and inheritance of cancer-predisposing genes only contributes to 4-5% of all breast cancer cases. Nevertheless, it is also vital to identify those women who are at high-risk of developing breast cancer so that they can make the choices to protect themselves and their family if they so wish.
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.
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.
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.
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.