Homologous recombination deficiency

Find out more about what homologous recombination deficiency (HRD) is and what it could mean for your treatment.

What is homologous recombination deficiency (HRD)? 

DNA (a chemical in our cells that tells the cells how to work and behave) is constantly being damaged and repairing itself within our bodies. When DNA is repaired, the process is called homologous recombination.

Homologous recombination deficiency (HRD) is when your body is unable to repair double strand breaks in DNA. This means that cancer cells have a harder time repairing themselves in people whose tumour tests positive for HRD. 

Until recently it was thought that HRD was caused almost completely by a mutation in the BRCA1 or BRCA2 genes. BRCA1 and BRCA2 genes (instructions made from DNA that tell the cells in our bodies how to work) are normally protective against cancer. This is because they produce proteins that help repair breaks in DNA. If these breaks aren't repaired and more breaks occur, this can lead to cancer. BRCA1 and BRCA2 mutations are changes in these genes that stop them from producing the repair proteins and means that healthy cells are unable to repair themselves. 

It's now understood that HRD can include a number of genes and it's been found that around half of women with high-grade serous ovarian cancer have HRD.  

What is the impact of a positive test for HRD?

If your tumour is positive for HRD, it means that certain treatments are more likely to be effective. One of those treatments are PARP inhibitors. 

PARP (poly ADP-ribose polymerase) is a type of enzyme involved in many functions of the cell, including the repair of DNA damage. In healthy cells, when DNA is broken or damaged, PARPs act as a repair crew to help fix the damage. This means the cell lives. 

PARP inhibitors are a type of targeted therapy that block the action of the PARP enzyme in cancer cells, which means they can’t repair DNA damage. 

The combination of being HRD positive (which blocks the first repair mechanism) and taking PARP inhibitors (which blocks the second repair mechanism) means that PARP inhibitors can be more effective than in people whose tumours aren't HRD positive. 

How will the HRD test be done?

In order to see if your tumour is positive for HRD a sample of your tumour is needed for testing. This sample of tumour can be taken during surgery or through a biopsy (a medical procedure that involves taking a small sample of body tissue so it can be examined under a microscope). 

This type of testing is called somatic testing. It only picks up mutations that happen within the tumour. It does not pick up germline BRCA1 and BRCA2 mutations (changes in cells that are inherited from parents and that do not have cancer) so a test for a germline BRCA mutation will need to be done separately.

HRD testing will be offered to women who are newly diagnosed with ovarian cancer.

Why will I be tested?

Your tumour being HRD positive means that you may be able to access different treatments. For women whose tumour is HRD positive, some drugs may be more effective. This type of treatment is sometimes called personalised medicine.