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Example clinical scenario

A 59-year-old woman is diagnosed with a grade-three oestrogen receptor (ER)-negative, human epidermal growth factor receptor-2 (HER2)-positive T2N0M0 right-sided breast cancer.

When to consider genomic testing

Constitutional (germline) testing

  • Patients presenting with early HER2-positive breast cancer may be eligible for constitutional (germline) genomic testing of the BRCA1, BRCA2, PALB2, ATM*, CHEK2*, RAD51C* and RAD51D* genes (*truncating variants and high-risk missense variants only) if they fulfil certain clinical criteria as outlined in the National Genomic Directory:
    • breast cancer <40 years;
    • bilateral breast cancer <50 years;
    • triple-negative breast cancer <60 years;
    • male breast cancer (any age);
    • breast cancer <45 years and a first-degree relative with breast cancer <45 years;
    • combined pathology-adjusted Manchester score ≥15;
    • single gene pathology adjusted score ≥10;
    • BOADICEA or CanRisk score ≥10%; or
    • Ashkenazi Jewish ancestry and breast cancer at any age.
  • Based on the available information and under current criteria, this patient is not eligible for NHS-funded constitutional (germline) genomic testing because she does not have early-onset disease.
  • The patient’s family history should be assessed to determine whether she would meet criteria for testing on the basis of her Manchester or CanRisk score. You should seek support from your local clinical genetics service if you are not confident in using these scoring systems.
  • The patient’s ethnicity should be established, as women of Ashkenazi Jewish heritage who have breast cancer are eligible for constitutional (germline) genomic testing irrespective of age at diagnosis because of the higher prevalence of certain founder BRCA1 and BRCA2 variants in this population.
  • Adjuvant PARP inhibitor therapy is not licenced for use in HER2-positive breast cancer.

Somatic (tumour) testing

  • Currently no somatic (tumour) testing specific to early HER2-positive breast tumours is available.
  • Somatic (tumour) testing may be available as part of clinical trials and is likely to become more widely available in the future.

What do you need to do?

  • Consult the National Genomic Test Directory to ensure that your patient is eligible for testing. You can also access a spreadsheet containing details of all available tests.
  • Decide which of the panels best suits the needs of your patient. For patients affected with early breast cancer, the options are:
    • R208 for constitutional (germline) testing in suspected inherited breast cancer; and
    • R216 for TP53 testing.
  • A record of discussion form is required prior to constitutional (germline) testing.
  • For DNA-based constitutional (germline) tests, an EDTA blood sample is required. Please refer to your local Genomic Laboratory Hub for details of test request forms and where to send samples.
  • 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.
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  • Last reviewed: 04/10/2023
  • Next review due: 10/04/2024
  • Authors: Dr Sarah Howlett
  • Reviewers: Dr Ellen Copson, Dr Terri McVeigh