Tumour BRCA & HRD Testing

Cancer: Solid Tumours

Homologous recombination deficiency (HRD) testing & tumour BRCA (tBRCA) genomic sequencing in ovarian carcinoma and related FIGO stage III and IV cancers

Homologous recombination deficiency (HRD), resulting from defects in the homologous recombination repair pathway and leading to genomic instability, is a common feature of HGSO cancers and is predictive of sensitivity to poly ADP-ribose polymerase (PARP) inhibitors. The evaluation of HRD status is currently best undertaken by HRD genomic instability testing in addition to BRCA1 and BRCA2 mutation (tBRCA) testing.

Homologous recombination deficiency (HRD) testing & tumour BRCA (tBRCA) genomic sequencing service is available to patients with advanced (International Federation of Gynaecology and Obstetrics [FIGO] stage III or IV), high-grade serous or endometrioid ovarian cancer (HGSO), primary peritoneal cancer, or fallopian-tube cancer. Hereafter referred to HGSO cancers.

This is being offered as a “package deal” in accordance with clause 18.1 of the Association of the British Pharmaceutical Industry’s Code of Practice, funded by a global co-promotion agreement between AstraZeneca & MSD and delivered in accordance with arrangements agreed with NHSEI through the NHS Genomic Laboratory Hubs.

HRD testing and tBRCA genomic sequencing is performed by Myriad Genetics Inc. in the United States.

Previously, the HRD/tBRCA service for HGSO cancer patients within the NE&Y GLH population has been delivered via the Manchester Genomics Laboratory. We are pleased to inform you that as from 19th April 2022, this service will transition to the Leeds Genomics laboratory.

All first line patients with newly diagnosed HGSO cancers are eligible for a tBRCA test as well as HRD testing through the above arrangement established between Myriad and Astra Zeneca. Relapsed 2nd and 3rd line patients who have not previously had any tBRCA or HRD testing are eligible for tBRCA testing, funded by NHS England when tested in a GLH Laboratory. The results of these tests can be used to identify patients who may benefit from PARP inhibitor therapy.

The eligibility criteria for HRD/tBRCA testing can be found on the NHS England website at:

NHS England eligibility criteria for HRD/tBRCA testing

Table 1.National Genomic Test Directory for cancer: Inclusions for HGSO

Essential Targets Test code Test Indication
BRCA1, BRCA2, SMARCA4 M2.1 Known high grade serous ovarian carcinoma or In cases of diagnostic uncertainty of small cell carcinoma of the ovary
HRD status (either positive for BRCA 1 and/or 2, or HRD positive) M2.5 Patient is eligible for first line treatment and has a diagnosis of high grade ovarian cancer

Please note that SMARCA4 testing is not currently performed as part of this service.  Please contact your local GLH laboratory if there is a clinical requirement for SMARCA4 analysis.

Requests for testing should be made via your local Cellular Pathology laboratory that holds the tumour tissue. Samples should be routed directly to the Leeds Genomics Laboratory at:

Leeds Genomics Laboratory
Genomic Specimen Reception, Bexley Wing (Level 5)
St James’s University Hospital
Beckett Street
Leeds, LS9 7TF

leedsth-tr.DNA@nhs.net (0113) 206 5205


Costs incurred following sample receipt by the Leeds Genomics Laboratory, including transport and test costs, are covered by Astra Zeneca for those samples sent to Myriad, and by NHS England for those samples where tBRCA only testing is undertaken in Leeds. Tissue preparation and transport costs prior to that are not covered by these commissioning arrangements.

Referral form

Please use the NEYGLH ovarian carcinoma referral form. Please ensure that the form:

  • Includes email addresses for your Cellular Pathology secretaries and pathologist. Results will be returned to the pathologist for integration into the full histopathology report and should not be acted upon out of context of those findings;
  • Clearly specifies which tests are needed;
  • Clearly specifies tumour cell nuclei as a percent of nucleated cells (in marked area if sections used).

Please only send tissue FFPE slide mounted sections (not blocks) with a marked H&E slide to the Leeds Genomics Laboratory.

Sample preparation is done in the local Cellular Pathology laboratory which holds the tumour blocks, prepared under standardised molecular laboratory protocols, which include a clean molecular microtome and histopathologist training/quality assurance in marking up and assessing specimens for molecular testing. However, if your local Cellpath lab is unable to undertake this type of preparation, it would need to make contractual arrangements with another Cellpath lab in order to provide appropriate material to the Leeds Genomics Laboratory for genomic testing.

The tBRCA/HRD testing service requires the testing of paraffin sections. Requirements are set out in the ovarian carcinoma testing referral form.  Please note that blocks and curls are not acceptable. Please adhere to the following guidance:

  • Please prepare 10 x 5uM thick unstained sections, air dried on mounted slides (no coverslips) with a corresponding marked H&E slide with regions of ≥30% neoplastic cells
  • Sections should be cut under conditions that prevent cross contamination from other specimens.
  • Please clearly mark the slides (where used) with at least 2 patient identifiers.
  • Please ensure that a return address is provided and that the Pathology review information section is completed.
  • Samples should be sent as soon as possible as the patient’s treatment might be dependent on the results of genetic analysis.
  • Cytology samples can be accepted for HRD and tBRCA testing. It is essential that cells and tissue fragments from the cytology samples are processed into agar/cell blocks, formalin-fixed and paraffin embedded. They should then undergo a Pathology assessment process as per tissue samples.

From 19th April 2022, samples from all eligible patients should be sent directly to Leeds Genomics Laboratory. Patient testing will be triaged as appropriate according to the request by the referrer. This will be one of two options:

  1. Where tBRCA and HRD testing are required, the Leeds Genomics Laboratory will send on all the appropriate samples and referral details to Myriad for a continuation of the existing tBRCA/HRD testing service, using the Myriad myChoice assay. The results of the BRCA1/2 and HRD tests will be returned by Myriad to the Leeds Genomics Laboratory. From this, an interpretive report will be issued by the GLH Genomics Laboratory to the appropriate referring clinician.
  2. For those patients where only tBRCA is required, testing for this for BRCA1 and BRCA 2 variants will be undertaken by Leeds using a customised NGS assay. As above, a report of the results will be returned by the GLH Genomics Laboratory to the appropriate referring clinician.

Newly diagnosed patients (1st line):

tBRCA sequencing & HRD test – Myriad will issue a report to the GLH Genomics Laboratory who will then issue a GLH supplementary interpretative report

Relapsed patients (2nd and 3rd line):

tBRCA sequencing only – the GLH Genomics Laboratory will issue a clinical report

Reports will include the following:

  • Referral reason
  • Result and result summary – with a clear statement on tBRCA and HRD status
  • Implications
  • Recommended action
  • Reports will also include any recommendations for clinical genetics follow-up/ analysis of peripheral blood to confirm germline status/extended testing as appropriate

National Genomic Test Directory

The 2020/2021 National Genomic Test Directory for rare and inherited disorders and cancer.

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