Results: Patient with ovarian cancer – constitutional (germline) BRCA variant identified

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 mutation is identified.

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 as well as ovarian cancer.
• Refer patient to genetics department for post-test counselling and to discuss cascade testing and onward management of risk.
• Refer patient to clinical genetics for 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.

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)