Interpreting results

Following analysis the testing laboratory will provide a summary of results as shown in the table below. BRCA1 and BRCA2 mutations are commonly classified using a 5-tier system. Results may inform patient management, prognosis and possibly subsequent germline testing (if not BRCA testing tumour and blood at the same time).1,22

In all cases when a significant variant is detected, the laboratory will provide a more detailed description of the mutation using current HGVS guidelines (http://varnomen.hgvs.org/). The clinical report may also include possible treatment options. Other information which is frequently included in laboratory reports include:1,23

  • Laboratory methods and sequencing platform used
  • The suitability of the sample for testing
  • Recommendations for genetic counselling
  • Follow up procedures if the test fails
  • Laboratory contact information 
  • Test limitations 

Classification of BRCA mutations:22

 

 

Variants of unknown significance

In some cases, testing will reveal a variant in BRCA1 or BRCA2 where there is insufficient evidence to determine if there is any effect on protein function.1,24 VUS are generally more common in less well characterized populations.24 However, it is important to note that these may have no role in the patient’s cancer.24 It should be noted that as new literature is published and databases updated, VUS may be reclassified over time. Your laboratory can provide additional guidance on whether additional samples are required.1,24

Test failure

Common reasons why BRCA testing may fail include insufficient neoplastic tissue and DNA degradation due to sample storage conditions, tissue fixation etc.1,24 In case of a test failure, either a new tissue sample will be requested, or blood testing will be suggested if a suitable sample cannot be provided.

Feel free to engage with your local AZ Diagnostics manager to help with these pathways and optimising samples for genetic testing.