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Example clinical scenario

A 44-year-old man is diagnosed with pancreatic adenocarcinoma. There is no significant family history of cancer. Routine constitutional (germline) testing of the BRCA1, BRCA2, CDKN2A and PALB2 genes is undertaken and a pathogenic BRCA2 variant is identified.

Impact of the genomic result

Constitutional (germline) BRCA variants in pancreatic cancer

  • Approximately 5% of unselected pancreatic cancer patients carry a pathogenic variant in BRCA1 or BRCA2, with a prevalence of up to 17% in patients with familial pancreatic cancer (depending on the definition criteria used).
  • On the basis of the phase-three POLO trial results, treatment with the PARP inhibitor olaparib has been licensed by the European Medicines Agency for maintenance treatment of adults with constitutional (germline) BRCA1 or BRCA2 variants who have metastatic adenocarcinoma of the pancreas and have not progressed after over 16 weeks of platinum treatment within a first-line chemotherapy regimen. However, this is not currently approved by NICE.

What do you need to do?

Management of the current cancer

  • Identification of a constitutional (germline) BRCA1 or BRCA2 variant (which is also present in the tumour genome) does not currently alter immediate clinical management guidelines within the NHS.
  • However, the patient may be eligible for a clinical trial involving treatment with a PARP inhibitor.

Management of the future cancer risk

  • Identification of a constitutional (germline) BRCA1 or BRCA2 variant means that the patient is at significantly increased risk of breast, prostate and possibly other cancers.
  • You should refer the patient to clinical genetics for post-test counselling and discussion of cascade testing and onward management of risk.
  • Issues around future cancer risk should be considered on an individual basis, and the patient’s prognosis from their pancreatic cancer should be taken into account.

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.
  • This means that first-degree relatives are at a 50% risk of carrying the BRCA variant. You should refer the case to clinical genetics to discuss cascade screening of at-risk relatives.

Note that the above advice is only relevant when a constitutional (germline) BRCA variant is identified. Somatic (tumour-only) 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 information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.

Resources

References for clinicians

For patients

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  • Last reviewed: 15/10/2023
  • Next review due: 15/10/2024
  • Authors: Beth Coad
  • Reviewers: Dr Ellen Copson, Dr Luke Hill, Dr Terri McVeigh