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Example clinical scenario

A 45-year-old woman is diagnosed with localised triple-negative breast cancer. There is no significant family history of cancer. She undergoes constitutional (germline) genomic testing as per national guidance and no pathogenic variants are found in BRCA1, BRCA2 or PALB2. She undergoes mastectomy and returns to the oncology clinic to discuss adjuvant treatment. She informs you that she has had a constitutional (germline) direct-to-consumer (DTC) genomic test which shows a pathogenic variant in the BRCA1 gene.

When to consider genomic testing

Constitutional (germline) testing

  • Women with breast cancer (primary or metastatic) are eligible for constitutional (germline) genomic testing of the BRCA1BRCA2PALB2ATM* and CHEK2* genes (*truncating variants only) if they meet at least one of the following criteria:
    • triple-negative breast cancer diagnosed <60 years;
    • breast cancer (grade 2 or higher) diagnosed <40 years;
    • bilateral breast cancer and both cancers diagnosed <50 years;
    • breast cancer diagnosed <45 years and a first-degree relative (FDR) with breast cancer <45 years;
    • Ashkenazi Jewish ancestry and breast cancer at any age; or
    • pathology-adjusted Manchester score ≥15 or CanRisk carrier probability of ≥10%. (These tools can be used to calculate risks. If you are not confident to do so, seek support from your local clinical genetics service.)
  • Women diagnosed with breast cancer ≤30 years or patients with triple-positive breast cancer (ER+/PR+/HER2+) ≤35 years are also eligible for testing of TP53. Testing can be taken contemporaneously with testing of other genes, after appropriate pre-test counselling.
  • Consider a referral to clinical genetics for any woman with breast cancer (primary or metastatic) who has a personal and/or family history of endometrial, thyroid, diffuse gastric cancers or non-cancerous features, such as cleft lip/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 ≥FDR/SDR has diffuse gastric cancer (≥one case occurred <70 years); or
    • two cases of lobular breast cancer <50 years, such as bilateral or multiple ipsilateral tumours.

What are the pitfalls of DTC testing in this situation?

  • High false positive rates have been reported for rare variants detected following analysis of raw DTC sequencing data by a third-party company. Variants identified in this manner should be validated in a clinical laboratory before any change in management is recommended. At present, however, validation of DTC results is not funded by the NHS unless the patient would otherwise meet criteria for germline genomic testing.
  • Conversely, a ‘negative’ DTC test should not replace the need for formal constitutional (germline) genomic testing in those women fulfilling eligibility criteria, as many DTC tests offer testing of only certain variants in certain genes rather than full sequencing (for example, some DTC tests will check only for the three Ashkenazi Jewish founder variants in BRCA1 or BRCA2, and will not detect the thousands of other potential pathogenic variants that have been reported in these genes). 

What do you need to do?

  • Do not assume that the DTC testing that has been done is complete or that the results are accurate.
  • No clinical action should be taken based on results from DTC testing.
  • Only results that have been obtained from a clinical diagnostic laboratory should be used to determine management or plan preventative strategies.
  • In this case, as an NHS diagnostic test has already been performed, it may be helpful to contact the NHS laboratory directly to confirm that no pathogenic mutations were identified. It may provide reassurance to both you and the patient.


For clinicians


For patients

Science Weekly podcast: The dangers of DIY genetic testing

Tagged: Breast cancer, DTC testing

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  • Last reviewed: 04/05/2022
  • Next review due: 04/05/2023
  • Authors: Dr Alison Berner
  • Reviewers: Dr Ellen Copson, Dr Amy Frost, Dr Terri McVeigh