Results: Patient with ovarian cancer and a constitutional (germline) BRCA variant
The identification of a constitutional (germline) BRCA1 or BRCA2 variant in a patient with ovarian cancer has implications for the clinical management of the current cancer and the patient’s future cancer risk; it should also trigger cascade screening in the wider family.
Example clinical scenario
A 64-year-old woman is diagnosed with high-grade serous ovarian cancer. There is no significant family history of cancer. Constitutional (germline) testing of the BRCA1 and BRCA2 genes is undertaken routinely and a pathogenic BRCA1 variant is identified.
Impact of the genomic result
Identification of a constitutional (germline) BRCA1 variant has implications for treatment of the patient’s current cancer, as well as for their risk of further primary cancers, and also has implications for their wider family members.
What do you need to do?
Management of the current cancer
- Identification of a constitutional (germline) BRCA1 or BRCA2 pathogenic variant (that is therefore also present in the tumour, or somatic, genome) means that the patient is eligible for first-line maintenance treatment with the PARP inhibitor, olaparib.
Management of future cancer risk
- Identification of a constitutional (germline) BRCA1 or BRCA2 pathogenic variant means that the patient is at significantly increased risk of breast cancer and other cancers as well as ovarian cancer.
- Refer patient to genetics department for post-test counselling and to discuss cascade testing and onward management of risk, including discussion regarding cancer surveillance/chemoprophylaxis and/or risk-reducing surgery, if appropriate.
Management of the family's risk
- The cancer risk associated with pathogenic constitutional (germline) variants in BRCA1 or BRCA2 is inherited as an autosomal dominant trait.
- First-degree relatives (males and females) are at a 50% risk of carrying the familial BRCA1/BRCA2 variant. Refer to clinical genetics to discuss cascade screening of relatives at risk.
Note: The above advice is only relevant when a constitutional (germline) BRCA1/BRCA2 variant is identified. Somatic (tumour) BRCA variants that are not present in the patient’s normal tissues have no implications for the patient’s future cancer risk, nor that of their relatives.
- Information about patient eligibility and test indications was 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.
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
Resources
For clinicians
- NICE: Guidance on genetic testing for patients with breast and ovarian cancer
- Public Health England: Protocols for surveillance of women at very high risk of developing breast cancer
References:
- Chandrasekeran D, Manchandra R. ‘Germline and somatic genetic testing in ovarian cancer patients‘. British Journal of Obstetrics and Gynaecology 2018: volume 125, issue 11, page 1460. DOI: 10.1111/1471-0528.15171
- Kuchenbaecker KB, Hopper JL, Barnes DR and others. ‘Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers’. Journal of the American Medical Association 2017: volume 317, issue 23, pages 2,402–2,416. DOI: 10.1001/jama.2017.7112
For patients
- Royal Marsden NHS Foundation Trust: Beginner’s guide to BRCA (PDF, 48 pages)
- Target Ovarian Cancer: Genetic testing and hereditary ovarian cancer – a guide for women with ovarian cancer and their families (PDF, 27 pages)