Presentation: Patient with a relative who has a pathogenic BRCA variant
If pathogenic variants in the BRCA1 or BRCA2 genes are identified in one of your patient’s first-degree relatives, your patient is at risk of having inherited a familial variant that predisposes them to certain cancers. Referral to clinical genetics services should be considered regardless of the patient’s gender.
At a glance:
- Hereditary cancer predisposition syndromes are caused by constitutional (germline) pathogenic variants within specific genes, such as BRCA1 and BRCA2.
- Most cancer predisposition syndromes follow an autosomal dominant inheritance pattern. This means that first-degree relatives of an individual with an inherited BRCA1 or BRCA2 variant have a 50% chance of inheriting the familial variant, regardless of their gender.
- Testing an unaffected relative for a familial gene variant is known as predictive or pre-symptomatic testing.
- Alert! Males who carry a pathogenic variant in BRCA1 or BRCA2 also have an increased chance of developing cancer.
Example clinical scenario
A 35-year-old man attends clinic and presents an email from his mother in Australia, which says that she has been diagnosed with a BRCA2 pathogenic variant.
Identifying those at risk of a genetic condition
- It is important to ascertain how your patient is related to the relative with the pathogenic variant. This will help confirm whether they are at risk of having inherited the variant.
- A common pitfall is to assume that because a variant in a particular gene (such as BRCA1 or BRCA2) is associated with a higher risk of female-related cancers (for example, breast or ovarian cancer), men do not inherit the variant or do not have an increased risk of cancer if they do. As illustrated in our dedicated BRCA1 and BRCA2 resource, this is not the case.
What should you do next?
- Patients at risk of having inherited the variant should be offered referral to their local clinical genetics service, who will provide access to information and counselling about testing.
- Include details of the affected family member in your referral to clinical genetics (for example, name and date of birth) so that the team can obtain the consent, reports and samples needed to proceed with testing should the patient wish.
- Including the relative’s details in a referral letter does not break confidentiality because the information has come from the patient, who is a third party.
- Upon referral, the clinical genetics team will ascertain which is the most appropriate family member to be tested. Testing of first-degree relatives in secondary care (including adult children, siblings and parents) will usually be offered sequentially to identify which family members may be at risk of carrying the familial gene variant and therefore the cancer-predisposing syndrome.
- For adult-onset cancer syndromes such as those associated with pathogenic variants in BRCA1 and BRCA2, predictive genomic testing is not typically offered to children until they reach an age at which they can legally provide their own consent.
- If a person carries a pathogenic variant that increases risk of a cancer predisposition syndrome, clinical management may include additional screening, risk-reducing measures (for example, lifestyle advice, medication and/or surgical intervention) and symptom vigilance.
- Individuals with a relative known to carry a pathogenic BRCA1 or BRCA2 variant may be eligible for additional screening recommendations, even if they do not wish to pursue predictive genomic testing.
- Predictive testing can generate feelings of despair or anxiety in those who have inherited the familial variant, and guilt in those who have not. Your patient may need additional support.
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
- Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
Resources
For clinicians
For patients
- Cancer Research UK: Family history and inherited cancer genes
- Macmillan Cancer Support: Family history, genes and cancer risk
- The Royal Marsden NHS Foundation Trust: A beginner’s guide to BRCA1 and BRCA2