Genomic testing for stage IV
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I agree Moth. I had a liquid biopsy recently and got nada. MO says that’s not unusual. They got circulating tumour cells but nothing actionable.
I understand your confusion regarding estrogen therapy at this point Candy. My MO indicated I am now resistant based on spread to my liver on Faslodex and Verzenio but he does want to try Aromasin regardless. We’ll see.
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Hi everyone, I'm new to this thread. I just got my FoundationOne test back and was very disappointed to see that my Tumor Mutational Burden was only 1Muts/Mb and no therapies or clinical trials were noted except for amplification of CCND1 which does not sound good. Therapies recommended for that were Verzenio but my insurance company has initially denied it because I had previously progressed on Ibrance after two years stable. I had progression about a year ago. I have been MBC since Jan. of 2017. My onc.said they will try to appeal for find someway to get it approved. I also see that my cancer has changed from ER+PR+HER- to ER+PR-HER. I read that this is not a good change. Has anyone had this happen and has anyone who tested with a low mutational burden found a treatment that has been helpful? My onc said that it's time to discontinue Xeloda and move on chemo, probably Halaven. It's been a tough week to find all this out especially since I've been battling a kidney stone. I have some plueral effusion in my lungs but can't feel any effects from it yet, so it's hard to think of coming to the end of the line as far as treatments and giving up. Would appreciate any encouraging thoughts on moving on to Halaven or dealing with results of genomic testing.
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Hi everyone. I have read most of this thread and have a few questions
1. Is IntClust a measureable test available or just analyzed in research studies? Also is it tested on original tumor, not metastatic?
2. For those who have had subsequent F1 (or other) studies, do you see your same mutations show up in addition to new ones?
I am leaving Xeloda after 15 months..great chemo, especially after finding the right dose. Onward to a taxane.
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SandiBeach, I just had the Guardant360 blood biopsy and compared the test from the year before. In the past year, my tumor load has slightly increased yet still remains low. In addition, I have progressed on 2 treatments (small progressions). The results look the same in comparison except that I now have enough of the PIK3CA mutation to qualify for Piqray. I just got a lung biopsy (my first biopsy in my lungs) and my tumor turned from ER+ to triple negative. We suspect that my liver (original ER+ biopsy) and possibly my other lung nodules remain estrogen positive considering they are currently responding to an oral SERD. So, despite a change in hormone receptors, my blood biopsy shows little difference as far as mutations. ~Kar
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KarPC, thank you!
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Not an urgent question here but if anyone knowledgeable feels like responding-
I didn’t have any genomic testing done at the beginning of treatment. My understanding is that it’s because I was HER2+, Stage IV deNovo and didn’t have surgery so no tissue other than my needle biopsy. When I asked about meeting with the GENETIC counselor, they said no to that too because no family history, older age, not TNBC etc.
So now I’m at a different cancer center. The doctor asked me a few weeks ago, did you have “genetic” testing, I said no, I didn’t fit the profile.
This week I was reading the notes in my patient portal and I saw that she sent my bone biopsy out for testing.
No one told me this. Anyway, there were results for PDL1 - negative. And then it says “NGS pending”. I googled NGS and came up with Next Generation Sequencing - which seems like the whole genomics panel for cancer.
I intend to ask about this at my next appt but I’m curious - it seems there are only two actionable mutations in this test anyway - ERBB2 which doesn’t matter, I’m HER2+ and responding to treatment. The other is the one where Piqray is indicated (PIK5 or something?). And PDL-1 positive is useful for immunotherapy? I think
I guess she just likes having this info on hand in case it’s needed but right now doesn’t seem it’s that useful.
If anyone has any input, especially if I am getting things wrong about mutations, etc....I welcome all replies!
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Add a somatic BRCA mutation which couldput a PARP inhibitor on the list of possible treatments.
Alpelisib is for PI3KCA.
Clinical trials addressing other mutations may show up on the report.
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Thanks, SP - PI3KCA that’s what I was trying to think of! Couldn’t quite remember it without looking it up
And I forgot about BRCA. Will be good to rule that out if I am in fact negative. I have sisters and nieces and we were worrying about hereditary factors in the beginning.
It will be good to have the info in my chart for the future,too, I guess.
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Something interesting about BRCA and some other mutations, is that they can be germline -- inherited, in every cell, or somatic -- just in the cancer cells. So if a genomic (NGS) test of the tumor shows it, then they do genetic testing of you to see which it is. That is how I found out about our family Lynch gene. It showed up in my Foundation One report, so I got genetic testing. Now my family can take extra screening and prevention steps.
I think a baseline genomic test can be useful. My first F1 showed very few mutations. Later ones, after progression on Ibrance + letrozole, showed the ERBB2 mutation. The timing indicates to me that that was how the cancer became resistant to I + L, and guided me to my current effective treatment.
Oh and another thing NGS tests can show is what treatments the cancer may be resistant to. For example an ESR1 mutation that would indicate resistance to some hormonal therapies.
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Great info! Thanks again! Curious to see these results
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just an update to my previous posts - results came back “QNS” - quantity of tissue not sufficient for testing. So no “baseline” genomic info for me.
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Hi all - I posted upthread on here about my Foundation One liquid biopsy from November 2020. When I had recent progression to an SCF node, I was able to get a tissue sample and decided to order a Caris test - the one that does whole exome and whole transcriptome sequencing.
Well, despite having 4 good cores from the tissue biopsy, the results came back that they didn't have sufficient tissue for any of the RNA testing, or half the DNA testing! So one lesson I would say from Caris is they seem to need a LOT of tissue. They are going to refund me for the tests that weren't performed, apparently. We'll see.
A few new things did come from the test. The only mutations that came out were RB1 and TP53 (both picked up by Foundation One), and PRKDC (not picked up on Foundation One). I had three other mutations in Foundation one and lots of amplifications - the Caris said it couldn't evaluate amplifications from my sample...
The other thing that came from Caris was I have high Loss of Heterozygosity (LOH). Apparently, even though I don't have BCRA1, 2 or PALB or any similar, I have the genomic scars that are produced by those genetic mutations. Which, according to Caris, means PARPis could work for me (I'm not so sure...). Has anyone read about Loss of Heterozygosity as a genomic marker?
My googling tells me that there are some signs a PRKDC mutation can make cancer more sensitive to immunotherapy - but I feel like I already have a bunch of things potentially sensitising me to immunotherapy (intermediate TMB, even this Loss of Heterozygosity). But not the only one that matters - I'm PDL-1 negative. I guess it's worth keeping an eye out for a clinical trial with a PARPi and immunotherapy at some point and who knows...
Anyway, happy to add to the general knowledge bank re our mutations and genomic scars...
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I don't have any knowledge to add, Phet, but I want to thank you for posting and educating.
Olma, bleh, I'm sorry you did not get any info. I had that happen once with a liquid biopsy. Tried again later when I was off chemo and had some progression, and got info.
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phet, LOH is now routinely tested for metastatic prostate cancer since FDA just approved Olaparib for metastatic prostate cancer with LOH features. If I were you, I would seriously look at a PARPi + immno trial. There is one current open for mTNBC with Olaparib + durvalumab. Please keep in mind though, if you use an immno now it would usually exclude you from future trials that use immunotherapy. So you need to choose your immno trial or approved treatment carefully.
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Phet, There are also reports that cancers that started out ER-positive and "converted" to ER-negative are much more sensitive to immunotherapy (like 50%) than either ER+(5%) or TNBC (15%). Two women whose metastatic breast cancers were cured or went into durable remission had that type of cancer, apparently those cancers are quite distinct from the other subtypes at the molecular level. So, I like Figtree's advice, a trial with PARPi & IO...
PS However, I have seen a lot of IO trials that do not exclude prior IO use, so long as its offered in combination with a different drug
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Thank you Cure-ious, Figtree and Shetland! It's interesting to know that LOH is now a biomarker for prostate cancer. It seems I always have biomarkers that *could* be a sign of something but no slam dunk. I'll still bring it up with my oncologist. I'm in the UK and at present the only trial with Parp and immuno is closed to recruitment but I'm going to keep an eye out. I also have the chance of coming to the US for a trial if it is promising so I'll keep an eye out there. Being TNBC (or low - 3 - ER+) I don't have many options so I am willing to try anything! Especially something that could bring durable remission - that's always the dream...
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Moth, thanks for this thread.
I received F1 report, bTMB 3, microsatellite- MSI high not detected (baited but not detected on test), tumor fraction cannot be determined (sample is not of sufficient data quality to confidently determine biomarker status). And plenty of codes called “variants of unknown significance” were detected which these variants may not have been adequately characterized in the scientific literature now, they become critically meaningful in the future.
Well I am impressed by this highly subtle language they used in this piece of work!!!!!
Please help me understand: what are these vus? And how this little information might be useful?0 -
So... variants of unknown signficance are mutations that we don't know what they mean.
They're not what's seen as typically normal genes but we can't link them yet to any specific pathological progresses. I think as these genomic tests keep gathering data and amassing large libraries of mutations and conditions that people develop, or ways their diseases behave etc, then with time, the variants might become associated with something and then eventually some VUS would become a known mutation which has a certain effect.. but I've also heard some geneticists say that probably a lot of mutations are not significant. They're variations that do not effect protein coding and so do not have any importance for the organism's growth or evolution.
by the way, there's a lot of the genetic code that is either largely dormant or apparently superflous - I think <10% of human DNA is what we think of as functional at this time...nobody knows what a lot of the other genes are doing.
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Great explanation, thank you so much Moth.
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Hello to all! I'm new on this thread so I may have quite naïve questions. I don't have genomic testing of FoundationOne or Caris. But I did oncogenes testing. During registration to this forum oncogenes testing is called genomic test or genomic array. But also no mentioning of F1 or Caris but Oncotype, Mammostrat, Mammaprint & Prosigna. Another possibility during registration was: 'A gene test wasn't done on the breast cancer'. 'Gene' test not 'genomic which is different from genetic' test. My testing doesn't have any of those mentioned names. However, method used was Next Generation Sequencing (NGS). It's described as full test of all gene groups related to BC. Nevertheless, I counted only 16 oncogenes, not 84 as in cases of some others. I checked that F1 for BC (meaning mentioning only 8 main genes) mentions 3 common oncogenes with my test (TP53, PTEN, CDHI or CDH1). I also tested for BRCA1 & BRCA2. But not for PIK3CA which would show if I'm eligible for Piqray (Alpelisib). So I confused a bit. So what's the difference between NGS genomic vs NGS genetic or gene testing? As I understand NGS is a way of doing test. But when it's called genetic & when genomic? Is it that in the beginning so called genetic test is done to detect main oncogenes of BRCA1 & BRCA2 & only then genomic test could be done additionally? How or under what conditions can I get testing for PIK3CA? Is it only in F1 or similar genomic tests? Patient must pay for e.g. F1 genomic testing or MO can order it? I'm de novo so I didn't have surgery so no tissue other than my needle biopsy from breast, CSF & additional blood from vein - I don't know what exactly was used for test. If anyone can clarify any of mentioned aspects, I welcome it! Especially if I'm getting things wrong or I'm writing in wrong thread.
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Spindi, normally the way I see the terms used is
Genetic: tests done on the person's DNA
Genomic: tests for on the tumor DNA
Do you know the company that ran your test? I'm thinking you had a genetic test looking at germline mutations.
And you also had Oncotype , is that right?
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DeNovo metastatic patients don't usually get oncotype or mammaprint tests because those are done to decide whether or not an early stager can benefit from chemo.
During my diagnosis, when they still had me at Stage 2, I wasn't even going to get oncotype because with a HER2+ tumor > 2 cm I was already a candidate for chemo.
I don't know exactly what genes they look at but I do know not everyone needs those tests.
And if you're in the US and your doctor orders F1 or similar testing, insurance usually does cover it. I didn't even know my oncologist was sending my samples out, so of course I was never asked to pay,as per my post above.
Also — “that in the beginning so called genetic test is done to detect main oncogenes of BRCA1 & BRCA2 & only then genomic test could be done additionally?“No these tests are independent of one another and you do not have to have BRCA mutations to be tested for PI3KCA or to benefit from Piqray
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Hi everyone
Can anyone help with genetic testing please?
My consultant referred me in the UK to the NHS genetics team as he felt I should be tested as I was diagnosed de novo at 37.
The genetics team have written to me to say they won't be sending my blood sample off as my questionnaire did not show enough evidence of family history of cancer.
I would still like it done, but not sure where to go?
Do I need to pay a private consultant to do the test?
Also I have been reading about the Pik3ca mutation but not sure if this mutation is picked up on genetic test or if its done separately?
Can anyone help??
Thanks
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HI Hamer,
NHS genetics testing is SUPER stingy, here are the current requirements:
You will only be eligible for NHS testing if more than one family member has developed breast or ovarian cancer - or been diagnosed very young - and the faulty genes have already been identified in a relative
So its a bit chicken and egg here - if someone has already had it identified then you are likely to be aware but if it hasn't been identified well then you could be BRCA positive which would have implications for your care, but they won't test for it because *see above*. Its annoying to say the least, especially if dx'd young. I got caught in this paradox because statistically with no family history I was unlikely to have the gene. Well, surprise! I did and if it wasn't for private coverage that wouldn't have been uncovered.
Youll have to go private for the testing and pay out of pocket which typically includes consultation with genetic oncologists and the bloodtest itself, which has to be sent off to a lab in the US. It won't be cheap - probably about £1000 or so, having had a quick look online. Any of the private breast hospitals offering this (HCA, Spire, etc) would likely be a good option though youll have to do some legwork to sort out a private pay package and cost. Make sure you are only getting BRCA1/2 testing and that they aren't doing testing way beyond that which you may not need.
Pik3ca mutation is a genomic test and one that would be done on the tumor itself, usually on progression.
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Hamer,
I’ll defer to sondra for advice on obtaining genetic testing in the UK. In the US, there is also screening based on similar factors that one needs to meet in order for insurance to pay for genetic testing. There is one other factor that will green light testing here. If you are of Ashkenazi Jewish descent you qualify for testing for BRCA genes. There are now over 30 genes that can be tested which can factor into higher risks for bc so, IMO, if you are going to self pay, you may want to consider those as well if the cost is not exorbitant. Take care
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Hi Sondra & exbrnxgrl
Thank you both for you replies.
I did have a feeling this would happen with the NHS, I must admit when they took the bloods 2 months ago I assumed they were being sent off but now they tell me they are keeping them in the lab!
I will definitely go private, I know it won't be cheap but I feel like I need to explore all avenues for future treatment. I won't rest if I don't check it.
Sondra my current treatment, Ribociclib and letrozole are working OK at the moment, fingers crossed this continues. If there is progression will the NHS fund the Pik3ca test or would I need to fund that privately too?
Thanks again your replies were really helpful.
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Hamer,
I have no idea what the cost of these tests are if you are self paying but the odds are high that no genetic mutations will be found.I should point out that genetic links to bc are the exception, not the rule. I can’t remember where I saw it but only about 15-20% of bc cases stem from a genetic mutation. Additionally, in terms of tx, genomic testing may be more informative than genetic testing.
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I think exbrnxgrl makes a good point about genomic testing ( like foundation, caris, tempus etc) might be better way to spend $ as it could identify more treatment options. Genomic testing will find both germline and somatic mutations..though I believe they don't differentiate between the two.
genetic testing will only identify a germline mutation & usually they screen fewer target genes
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I don't know about funding a test for that specific mutation as Piqray hasnt been approved for use in the UK yet. I know of only one person who was on that drug and it was via a trial two years ago, so probably not worth worrying about too much at the moment!
I believe that there is genomic testing offered on progression, but that is something to confirm with your consultant. So at that point if you were tested and the BRCA gene came up it would influence your treatment path anyway whether you knew about it before or not. Moth and exbrnxgrl both make good points about other things to consider, but I would definitely first confirm with the consultant about the procedure, specifically genomic testing, to inform treatment decisions at progression and then go from there.
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Thank you all for your replies on this, You have been really helpful.
Take care
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