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Example clinical scenario

A 44-year-old woman is diagnosed with a grade-two oestrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, T2N0M0 left-sided breast cancer.

When to consider genomic testing

Constitutional (germline) testing

  • Patients presenting with early ER-positive, HER2-negative breast cancer are eligible for constitutional (germline) testing of the BRCA1, BRCA2, PALB2, RAD51C*, RAD51D*, ATM* and CHEK2* genes (*truncating and high-risk missense variants only) if they meet at least one of the following criteria:
    • diagnosed <40 years;
    • presence of bilateral breast cancer and both cancers diagnosed <50 years;
    • breast cancer diagnosed <45 years and a first-degree relative with breast cancer diagnosed <45 years;
    • the patient is male;
    • combined pathology-adjusted Manchester score ≥15;
    • single gene pathology adjusted score ≥10;
    • BOADICEA or CanRisk score ≥10% (these tools can be used to calculate risks; if you are not confident in using them, seek support from your local clinical genetics service); or
    • Ashkenazi Jewish ancestry and breast cancer at any age.
  • Treatment with adjuvant olaparib (a PARP inhibitor) is available via the Cancer Drugs Fund for patients with a constitutional (germline) BRCA 1 or BRCA2 variant and a high-risk ER-positive, HER2-negative early breast cancer who have completed standard neoadjuvant chemotherapy treatment. For this indication, ‘high risk’ is defined as:
    • patients who have not had a pathological complete response following neoadjuvant treatment, and whose clinical-pathologic scoring system incorporating oestrogen receptor status and nuclear grade (CPS + EG) score is ≥3; and
    • patients with ≥4 positive axillary lymph nodes who have not received neoadjuvant chemotherapy following surgery and adjuvant chemotherapy.
  • Patients diagnosed with breast cancer ≤30 years are also eligible for constitutional (germline) testing of TP53. Testing can be taken contemporaneously with testing of other genes (using the same sample), after appropriate pre-test counselling.
  • Consider referral to clinical genetics for any woman with breast cancer (primary or metastatic) who has a personal and/or family history of endometrial, thyroid or diffuse gastric cancers, or non-cancerous features such as cleft lip or palate, macrocephaly, mucocutaneous lesions or a history of intussusception, which may be features of an underlying syndromic cause of breast cancer predisposition.
  • Women with lobular breast cancer may be eligible for CDH1 testing if they meet one of the following criteria:
    • lobular breast cancer <70 years and diffuse gastric cancer <70 years;
    • lobular breast cancer and one or more first- or second-degree relative(s) with diffuse gastric cancer, where one or more cases occurred <70 years; or
    • two cases of lobular breast cancer (such as bilateral or multiple ipsilateral tumours) <50 years.

Somatic (tumour) testing

  • Patients with ER-positive, HER2-negative, lymph node-negative early breast cancer with an intermediate risk of recurrence are eligible for multi-target expression array testing of their tumour. This may provide additional information to guide decision-making around adjuvant chemotherapy. The most common tests available are Prosigna, Oncotype Dx and Endopredict, which are approved by NICE. The tests generate a score that suggests the additional benefit from adjuvant chemotherapy. The choice of test used will depend on local arrangements.

What do you need to do?

  • Consult the National Genomic Test Directory to ensure that your patient is eligible for testing. You can also consult a spreadsheet containing details of all available tests.
  • Decide which of the panels best suits the needs of your patient.

Constitutional (germline) testing

  • For patients affected with early breast cancer, the constitutional (germline) genomic testing options are:
    • R208.1 and R208.2 for constitutional (germline) testing in possible familial breast cancer;
    • R215.1 and R215.2 for testing related to CDH1 in lobular breast cancers; and
    • R216 for TP53 testing.
  • A record of discussion form is required prior to constitutional (germline) tests.
  • For DNA-based constitutional (germline) tests, an EDTA blood sample is required. Please refer to your local Genomics Laboratory Hub for details of test request forms and where to send samples.

Somatic (tumour) testing

  • The somatic (tumour) testing options are M3.2, M3.3 and M3.4 for tumour profile tests of intermediate-risk ER-positive, HER2-negative early breast cancers (these are multi-target expression array tests).
  • The genomic tests described above are performed on formalin-fixed breast cancer tissue samples. You should contact your local cellular pathology department to confirm local contract and request arrangements.
  • 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: 08/10/2023
  • Next review due: 30/04/2024
  • Authors: Dr Sarah Howlett
  • Reviewers: Dr Ellen Copson