Mutation testing?

[Loverosie]

Hi everyone, i was wondering if any of you have had their tumours tested for mutations for targeted immunotherapy? I stumbled upon a company called oncologica last night who do the test for £2000. I am going to speak to my oncologist about it but i wondered if anyone has had it done and if so has it helped? Thanks Jane

[Sh-x]

I am just starting treatment for recurrence, I have a new consultant who is sending my original tumour for testing. This will take approximately 3 months and is done under NHS. Will let you know how it goes. xxx Shona

[Loverosie in reply to Sh-x]

Thank you Shona, do let me know. Where are you being treated if you dont mind me asking? X

[Sh-x in reply to Loverosie]

I’m at the Beatson in Glasgow.

[Maus123]

Hi Jane. I love the concept of individual tumour testing, but would only do it under a major hospital or your oncologist's guidance. My own oncologist specializes in immunology research to fight OC, and he advised me last week to wait a bit longer, as the research is still in early stages.

I believe it's just too easy for shady 3rd party businesses (not saying this one is, mind you) to exploit our fears, with a questionable result. However, if your hospital or oncologist offers it, I'd go for it.

All the best. Maus

[Loverosie in reply to Maus123]

Hi matus, I'm at Christies and they are doing some clinical trials around this which i am going to look into. I am though going to open a conversation about it with my team as this seems to be the way things are going. I have learned that all our cancers are very different yet we all seem to receive the same treatment which doesn't make sense really. Targeted therapy also has less side effects as it is aimed directly at the mutated gene rather than healthy cells which also makes alot of sense. Jane x

[Maus123 in reply to Loverosie]

Oh that sounds safe then, since it's done at the Christies. Yup, I'd definitely consider the opportunity under their oversight. My onc says the same. Best of luck on the trial. Maus

[RonLitBer]

I am not able to speak about the firm you are asking about. I do think that tumour testing should be a routine procedure covered by public health and we should advocate for that. One of the things that testing your tumour will tell you is what mutations the tumour has. This is different than hereditary mutations which can be passed on to offspring. One example of a finding that is very important is your tumour might be "BRCA-like" which means that you would perhaps do well on a PARP. Typically they use tissue from your initial debulking. However, if you have had treatment things change and your tumour changes so if no new tumour sample is used it may not reflect a current situation. Tumours that are not BRCA-like initially can become so. Similarly with a biopsy. It only gets at a small part of a tumour which may not reflect things as they are. These are just some limitations. And a bit of another roadblock is that even though they may find a mutation in your tumour there may not be anything available (any targeted treatment) for it. An example is that many women with high grade serous have a TP53 gene mutation (that affects the making of protein p53) but even though there has been much research and study devoted to this gene there is nothing available to address the varied mutations it may carry (missense, frameshift, nonsense, etc.). There are clinical trials addressing the mutation but I have not heard much about them recently. About 50% of all cancers have a TP53 gene mutation in their tumours. Again, this is different than having a TP53 mutation that is a germline mutation which would make it a hereditary mutation carried by each cell in your body rather than just in the tumour.

[Loverosie]

Thanks ron, very informative. I agree it should be the standard on the nhs. My original OC was a borderline 1c of which there are samples available also on reccurence i had biopsies taken before i had any treatment so am i correct in sumising that those samples may be useful for mutation testing or now I've had 6 cycles of chemotherapy will the tumours have changed? I find it quite complicated but you seem to know alot about this area. Are you a a patient or involved in some other way? In the US they do mutation testing as first line treatment. Regards Jane

[RonLitBer]

I see your cancer is mucinous which often has BRAF mutations but also TP53.

[RonLitBer]

It is very complicated and I find it an uphill struggle to get informed. There is not much education available. I am not in the US but in Ontario Canada and like you am suffering with this disease. I can't tell you if your tumour has changed because of treatment but treatment can change tumours and you can find out things about your tumour that may be valuable. Tumour testing is important because while they often test for hereditary mutations (typically BRCA for ovarian) there are differences between the two. There should be some tumour available from your debulking and biopsies that can be used to do tumour testing to find out what mutations your tumour may have. The bonus of having mutations in your tumour rather than hereditary mutations is that they are not going to affect offspring. The results can guide treatment but many times you kind of come up blank meaning that there is no actionable mutation. This happens with both hereditary and tumour tests. The example I gave was TP53. I am aware that my tumour has that mutation and I know what kind it is and where it happens on the gene. I know that no p53 protein is being made by my tumour (so no tumour suppression happening) but it is information that is not really something I can do much with. That is not to say that they will not find something actionable in your tumour.

[SCWI]

Hi Jane

I had my original tumour tested for a mutation earlier on this year on the advice of my second opinion professor and it came back positive for some type of BRCA mutation although I tested negative for this with the gene test. I don’t know a lot about this and Ronlitber knows much more about it than I do. As a result following carbo Caelyx I have just started the parp Inhibitor Olaparib. I am lucky to have health insurance and I think they footed the bill for the tumour testing. I had to push my team to do it though and I’m glad I did. What I don’t understand is whether the mutation came first and caused the tumour or whether it came after the tumour. This is a very complex subject! I think Oncologica is a reputable company but I am not sure if they did my tumour testing as it was done by my team.

I hope you manage to get it done. All best wishes, Sophia

[Loverosie in reply to SCWI]

Thats great Sophia, just what i was hoping to hear. I have also seen a geneticist who on my family history alone has not tested me for Braca, they are testing for lynch syndrome. It really is a minefield this subject but i feel it holds the key to longjevity but the problem with OC is that we are all recieving treatment in ordered to keep going and the treatment changes the mutation as i understand it. I am goung to have the discussion with my team and if they are on board in regards prescribing the indicated treatment and if it is not possible on the nhs then i will have to rob a bank because i just feel it's the right thing to do. Sophie Sabbage talks alot about following your instincts and this is the first time I've had one, an instinct, that is. Your comments have also helped me so thank you very much Sophia, sending all my positive thoughts that your treatment is beneficial xxx

[SCWI in reply to Loverosie]

Thanks Jane. Well done, you sound really positive and determined, keep on at your team until you get the testing, hopefully it may open up options for you as it did for me, and new things are happening. Ask them if there are any trials too if the NHS won’t fund it.

Keep us posted.

[Loverosie in reply to SCWI]

I have emailed my consultant's secretary asking all that you have mentioned. I will post the reaction and if i go ahead. Xxx

[RonLitBer]

Yes Sophia, the "gene test" would test for hereditary germline mutations. This is why a tumour test is a good thing to have done as it will give you information about tumour mutations which are called a somatic mutation. If it is only in your tumour it does not affect your offspring. If you have a tumour that is BRCA-like or has BRCA-ness it will give you some indication that you would likely respond to PARPs better than those without BRCA mutations (either germline or somatic). If the mutation is in the tumour it did not cause your cancer.

[SCWI in reply to RonLitBer]

Thanks very much for that information Ronlitber, it’s more than my oncologist told me, at least in layman’s terms. I hope there is a form of targeted therapy coming up to help you. Best wishes.

[coksd]

I'm having the test done in January and then hope to start immunotherapy, I only had an original biopsy of histology plural fluid and that didn't have sufficient PDL1 to test, the test is 1800euro in Dublin I need to have a new biopsy taken.

[RonLitBer]

coksd, I originally posted this on the Inspire site.

I thought this was an interesting article providing some explanation regarding why some patients in spite of low levels of PD-L1 on their tumours have been found to respond to anti-PD-1 or anti-PD-L1 therapy. It is fascinating and means that tumours do not need to suppress T-cells in close proximity.

parkerici.org/2018/08/15/a-...

[Lymetree]

Hi Loverosie, My mucinous is being tested under NHS because thèy thought the origin was ovarian? After a debulking op they then said it's primary site was small intestine? Now further tests are being done because they are not entirely sure about that?! You are right in thinking that they need to pinpoint its exact origins to get an accurate DNA profile for chemo. I'm not sure how long they are prepared to leave me without chemo while they try to get to the bottom of it?

Best Wishes yours will be sorted on NHS too? Maureen

[Loverosie]

Thanks Maureen, do let me know how you get on. When was your surgery? They do tend to give you a few months after to recover. All the best Jane