Germline BRCA awaited.

Hi,Can anyone say what the above actually means? Is it to find out if I am BRCA mutated or BRCA not mutated my letter says that I am HRD negative tumor.

Thanks very much for any helpful replies.

[Goingwiththeflow]

Hi @Rita44,

It means that they are checking for a BRCA mutation in your blood sample. From what you said, your tumour tested negative for BRCA (HRD mutations- homologous recombination deficiency mutations - include BRCA mutations) so now the oncology team is looking to see if you carry a BRCA mutation in your genes.

A person can carry the mutation in their genes but not in their tumour tissue or can have it in their tumour tissue but not in their genes or can have both.

If it is in the tumour tissue, it is called a somatic mutation. If it is in the blood sample (in the person's genes) it is called a germline mutation.

I hope that helps!

[Goodgirl98 in reply to Goingwiththeflow]

I am brca positive but did not know this. Thanks for elaborating.

[soyoonsoy]

Germline BRCA mutation means that every cell in your body has the mutation because you inherited the mutation from either of your parents. They used blood cells to test for this, since they are easy to collect. Somatic mutation is that only your tumor cells carry the mutation but the cells in the rest of your body do not. This has to rely on biopsy samples of your tumor to determine the outcome.

[Hidden]

Hi,

Thanks very much for those helpful clarification replies.

Having started Caelyx (chemo) just 3 weeks ago for 6 cycles and then afterwards I'm to start with Olaparib.

Evidently Olaparib works better if the patient is BRCA mutated regards their tumors, however like some patients I am not mutated in tumors.

My main question, as I am awaiting a germline blood test result for any gene mutation, and I'm found to have or not have a mutation in genes.

Will treatment later with Olaparib, be as effective as patients with BRCA tumor mutated.

I hope I have expressed my self as concise as all your replies I received.

Rita44

[soyoonsoy in reply to Hidden]

Just to add a bit more to add, BRCA1/2 are genes involved in DNA repair. Whenever DNA replicates in accordance with cell division, it normally generates breaks along the chromosome, and we have a built-in system to repair the break; otherwise, it could lead to accumulation of unwanted mutations that can develop into tumors. BRCA are such genes. So, when BRCA is mutated, it failed to repair the breaks, potentially leading to accumulation of cancerous mutations. PARP is another DNA break repair enzyme, but when one strand of the DNA has breaks, in contrast to BRAC which repairs when both strands are broken. An issue is once one strand of DNA is broken, it could easily lead to breaks of both strand. So, PARP inhibitor is in a way blocking a step before double strand breaks that has the high potential to generate new mutations whenever cells divide.

My tumor doesn't have BRAC mutations but HRD positive, so I was given PARP inhibitor, but it didn't work for me. For non-BRAC carriers, it appears to be somewhat effective if your tumor is still responding to Carboplatin. I tried PARP inhibitor after my tumor no longer responded to Carboplatin.

[Hidden in reply to soyoonsoy]

Hi,Interesting what you write, I become confused not so much your informative post, but generally most on answers on Google.

Tell me your up-to-date events and which Chemotherapy you've started ?

Are you later to be prescribed a combination PARP?

Thanks ...

Rita44

[soyoonsoy in reply to Hidden]

I was given Rucaparib, which didn't work, then I didn't try other PARP inhibitors again. This was after trying carboplatin and paclitaxol for the recurrence.

[Goingwiththeflow]

Hi Hidden

I'm in Canada, and here Olaparib is only approved for patients (maintenance treatment in the frontline and recurrent setting) who have a BRCA mutation (either germline or somatic), based on the clinical trials indicating that Olaparib was particularly beneficial for patients with a BRCA mutation.

In Canada, if a patient does not have a BRCA mutation, they receive Niraparib for frontline maintenance.

[Hidden in reply to Goingwiththeflow]

Hi,

Thank you for your response.

As I wrote earlier having recently starting Caelyx (chemo) just 3 weeks ago for 6 cycles and then afterwards I'm to start with Olaparib.

From what your saying 'Olaparib' isn't the best treatment outcome regards BRCA not mutated, I will take this up at my next face-to face with Oncology meeting and get some clarification, my PARP treatment is a few months away, so I've lot's of time to discover more.

On checking our NHS website an associated PARP called 'Durvalumab' given along with 'Olaparib' is another recommendation for those who are BRCA negative.

Another question, as I, and of course other patients are waiting for Germline BRCA results

is it possible to have a negative result in Germline BRCA as well I wonder.

Thanks much.

Rita44

[OvacomeSupport Partner My Ovacome Team in reply to Hidden]

Hi Rita44,

Thank you for posting about your experience and question here. Some of our members have already posted helpful responses.

In England under the NHS, Olaparib is only available to those who have BRCA1 or BRCA2 mutations. Your germline testing will identify whether you test positive for the BRCA mutations in your genes, and your clinical team will then be able to identify whether you can be offered Olaparib.

If you are found to not be positive for the BRCA mutations in your genes, your clinical team may be able to look at treatment with a different PARP inhibitor drug, such as Niraparib, depending on your eligibility for these.

Ovacome have published a booklet on targeted therapies, including PARP inhibitors, which you can access here: ovacome.org.uk/targeted-the.... This contains further information on how these treatments work as well as eligibility criteria. We can also post a copy of this to you, free of charge, if you prefer?

I hope that the results of your germline testing for a BRCA mutation and the resulting discussions with your clinical team will give you a clearer picture of which treatments may be available to you.

In the meantime, if you have any further questions or would like to talk anything through, please do give our support team a call on 0800 008 7054, or send us an email at [e-mail]. We are available from Monday to Friday, 10am - 5pm.

Best wishes,

Alice - Ovacome Support

[Hidden in reply to OvacomeSupport]

Hi,Alice, thanks very much for the reply and your helpful online links.

Rita44

[Goingwiththeflow]

Hi again,

I did some research on durvalumab. There was a phase 3 clinical trial that tested the addition of durvalumab to bevacizumab with or without olaparib, in patients without a BRCA mutation.

In the report from the 2023 Annual meeting of ASCO (American Society of Clinical Oncology) they said:

"The phase 3 DUO-O clinical trial found that adding the immunotherapy drug durvalumab (Imfinzi) and the targeted therapy drug olaparib (Lynparza) to standard treatment for people with newly diagnosed, advanced, high-grade epithelial ovarian cancer without a BRCA mutation delayed cancer growth and reduced their risk of death. "

Here's a link to the ASCO meeting report:

cancer.net/blog/2023-06/asc....

If I am understanding your question, yes it is possible to not have the BRCA mutation (be negative for the mutation) in germline testing.

What is important to understand is that the BRCA mutation is just one of the mutations that fall into the category of HRD mutations. HRD means homologous recombination deficiency, which means that cells with HRD have difficulty repairing double strand breaks in DNA, which is what makes these cells more susceptible to the impact of PARP inhibitors.

All patients with BRCA mutations would be considered HRD positive, however, a person can be negative for the BRCA mutations and still be HRD positive.

And the good news from the trial is that the addition of durvalumab to olaparib and bevazizumab increased survival time even for patients who were HRD negative.

From the ASCO report:

"What does this mean for patients? Adding durvalumab and olaparib to standard treatment for people with newly diagnosed advanced high-grade epithelial ovarian cancer that does not have a BRCA mutation may help delay cancer growth and reduce the risk of death, including for those whose cancer does not have HRD."

I know there's lots to learn - I spent a LOT of time when I was initially diagnosed getting my head around all of the information. I found it very hopeful to know that there are ongoing clinical trials testing new drug combinations - it makes me hopeful that there will be options available should I have a recurrence.

I was really terrified when I was first diagnosed - so I can understand if you're feeling that way too. Getting all of the information for possible treatment options, especially early on, is really wise.

Here in Canada it takes a while for new treatment options to be approved, not sure how it is where you live. That being said, it is always possible to lobby hard for what you want with your oncologist, and the more informed you are, the better.

[Hidden in reply to Goingwiththeflow]

Hi,

I had a rewarding experience reading your post especially over the PARP combinations outcomes, let us hope we negatives can all benefit from them in the coming future, not for getting the positives, naturally!

I continue to be fairly comfortable on my 24 days into my first Caelyx (chemo) although I have a worry as it's my first drip, that I'm not sure (didn't ask) what percentage of the full amount I have received.

If it turns out the full tank? I will be more solaced, in knowing possibly I can managed all expected side effects, but it's the first of six? OMG - Oh well ! Bring it on.

Thanks much

Rita44

[Goingwiththeflow]

I'm happy to hear that treatment is going well for you so far!

Exactly how I felt during chemo: bring it on!