Originally posted on the My Ovacome forum 18 November 2020. This post was last updated 18 August 2021

In this blog post we’ll be looking at BRCA mutations in more detail. As we mentioned in our first post in our Hereditary ovarian cancer series, our cells produce proteins that help to repair damaged DNA, which could otherwise cause a cell to multiply out of control and form a tumour. If the gene for one of these proteins has a mutation, the protein may not work properly or at all. DNA damage is therefore more likely to accumulate, so the cell can become a cancer cell.

One of the ways in which cells repair damaged DNA is called homologous recombination. You can watch a video about the different ways for cells to repair DNA damage, including homologous recombination here. 

There are a number of different genes which, if mutated, can reduce a cell’s ability to carry out homologous recombination. This is called homologous recombination deficiency, or HRD. BRCA1 and BRCA2 mutations are both types of HRD. Other genes involved include ATM, ATR, RAD 51, and PALB2. HRD was one of the topics discussed in our research update webinar with Dr Rowan Miller, which you can watch at Ovarian cancer webinars | Ovacome.

In April 2021 NICE included HRD status in their decision on the availability of bevacizumab and olaparib in combination as first line maintenance treatment. You can read more details on this decision here

Mutations in the BRCA1 and BRCA2 genes increase the risk of breast cancer and ovarian cancer. The lifetime risk of a woman with the BRCA1 mutation developing breast cancer is 60-90% and 40-60% (rising from the age of 40) of developing ovarian cancer. For women with the BRCA2 mutation, the lifetime risk of breast cancer is 45-85% and of ovarian cancer (rising from mid- to late forties) of10-30%. The mutations also increase the risk of breast and prostate cancer in men.

You can find more detailed information about the risks for carriers of these mutations hereThe Ovarian Cancer Action risk tool can be used as a guide to your own risk level based on your family history and can be found at Hereditary Cancer Risk Tool | Ovarian Cancer Action.

If you’re diagnosed with high grade serous ovarian cancer, you will meet the criteria for BRCA testing on the NHS. If you don’t have high grade serous ovarian cancer it is still worthwhile having a conversation with your team, as sometimes testing of any non-mucinous ovarian cancer is possible. It’s important to talk to your team about BRCA testing, as the results can affect your treatment options.

This is because the PARP inhibitor olaparib is currently only available to people with BRCA mutations and, at the time of writing this post, is the only PARP inhibitor available as first line maintenance therapy. PARP inhibitors must be started within eight weeks of your last cycle of chemotherapy, so testing needs to happen early enough for the results to come back in time.

If your BRCA test is positive, your team will discuss with you whether olaparib would be a suitable treatment for you and, if so, help you to decide whether you want to take it. If your test is negative, you won’t be eligible for olaparib but, depending on your diagnosis and medical history, you may be able to take a different PARP inhibitor either through your treating team or as part of a clinical trial.

PARP availability has been changing in recent years, including some changes to treatment due to Covid, so it’s important to ask your team for the most up to date information. We posted previously about PARP inhibitors and their availability at In focus: targeted therapies - PARP inhibitors - My Ovacome (healthunlocked.com).

You can find more information about BRCA mutations, their risks and testing for them at:

A beginner's guide to BRCA1 and BRCA2 (shared-d7-royalmarsden-publicne-live.s3-eu-west-1.amazonaws.com)

Testing for the BRCA gene fault | Ovacome

Predictive genetic tests for cancer risk genes - NHS

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