Guardant 360 testing
I didn't see a top for the Guardant testing so I thought I'd start one.
Does anyone know what it means when the first Guardant test showed a PIK3CA mutation, and then ten months later, it doesn't show that?
I might need to change my treatment if I no longer have this mutation!
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Dulcea- Thanks for starting this thread, I think it will be very useful. I did have a (rare) mutation, SF3B1, on a Foundation One test in 2021, then not picked up by Guardant in 2023, but appeared again on a Guardant test this year, but not on the front page, rather in the category of Variants of Unknown Significance. I looked it up and the mutation is in a cancer hotspot, and it creates cancers with a BRCA mutant environment/phenotype, so it could be informative.
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That's interesting @cure-ious . I wonder why they show up sometimes and not others.
The doctor initially informed me that the mutation showed up on my tissue testing, not the blood biopsy. I confirmed that two blood biopsies showed different results and messaged her. I am waiting for her response.
I have no idea if mutations come and go or if the medication I am taking affects the outcome of the biopsy or if it's there once, it's always there. Honestly, I'd rather not know this much about cancer mutations, but here I am.
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dulcea, in my case, Tempus liquid biopsy showed 1.4% ESR1 mutation, and 9 months later, Guardant reported 0.3%. I believe this decrease might be due to the effect of the med (Elacestrant). I think liquid biopsy results are helpful to understand the mutations, but tissue biopsies can provide more accurate details. so I requested a new tissue biopsy for further testing, hopefully in a few weeks I am able to report what happened to the mutation! my MO might have mentioned that even if the mutation decreases it could still indicate resistance to the med or the resistance to Elacestrant(?).
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Thanks @snow-drop . Yes, my tissue biopsy showed an ESR1 mutation that the liquid biopsy did not show, so I agree with you there.
As I understand it, the ESR1 mutation makes an aromatase inhibitor null and not work. Which makes sense with me since the arimidex (anastrozole) didn't work, hence the stage IV diagnosis. This makes me think that people with early breast cancer should have these liquid biopsies to see if they have that mutation and whether or not the AI will even work.
My MO replied with an answer about my situation. She is going to check with my second opinion doctor who practices at a teaching hospital because she's never seen this situation before! Ugh! I hate being special.
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Dulcea, I think in my case, the mutation may have been there all along, because the middle Guardant test did not have a page listing all the Variants of Uncertain Significance (or at least, I never got it). But I have heard of situations where a mutation disappears and reappears, maybe there's some glitchiness in the testing?
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I read that another way that cancers become resistant to CDK4,6i is by increasing the tumor mutation burden (TMB) (listed on the bottom of the front page of Guardant)- my numbers have gone up and I am resistant to both Verzenio and Ibrance. Anyone else seen this happen?
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Maybe I'll go read that big Guardant testing report again. My original MO told me the ESR1 mutation means the AIs won't work, which was not a surprise to her since I was diagnosed stage IV. I also confirmed it with my new MO who was going to change me from Faslodex to Aromisin but I reminded her of the ESR1 mutation and she agreed that I should stay on the Faslodex due to that. I'll put that question on my list for next time though. We need a topic on here for mutations. I know there are some very smart ladies on here who know all about this stuff!
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There are reports that certain PI3KCA (helical domain) mutations can increase tumor mutation burden, but also DNA repair deficiencies and other ways that involve the APOBEC enzymes- if the number goes high enough, immunotherapy becomes an option
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053638/
https://www.sciencedirect.com/science/article/pii/S0923753419406984
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PIK3CA was found to be mutated in 68.6% of hypermutated tumors with a dominant APOBEC signature versus 37.6% of hypermutated tumors without a dominant APOBEC signature (P =1.63 × 10−5, q = 0.015). The proportion of PIK3CA mutations in the helical domain were significantly enriched within hypermutated tumors with a dominant APOBEC signature (47.3% versus 25.0%; P = 0.01) and mutations in the kinase domain were enriched in hypermutated tumors without a dominant APOBEC (P = 0.19).
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@cure-ious clearly you are one of those very smart ladies out there doing research and helping us all.
That's interesting about the PIK3cA tumor burden and immunotherapy. Alas, I am the opposite with possibly no longer having the mutation according to Guardant. It's also interesting about he tumor burden increasing so much that it makes you resistant. When yous say resistant, does that mean you had progression on them?
I did go back and read my recent Guardant result which did not detect any mutations. It actually says right on the report that it could be due to "early stage, low volume disease, patients responding to therapy, and/or patients with stable disease". I hope that's the case!! I am a little relieved. It does suggest correlation with repeat Guardant with plasma or tissue sample.
It also says "The absence of detectable somatic alterations in circulating cell-free DNA does not preclude the presence of of somatic alterations in the tumor."
I am a little concerned with my MO who needs to go ask someone though. Has she never come across this before?
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Interesting thread and answers!
Also from what I understand the tumor may not be all etherogeneous, so depending where it been sampled it may variate.
I'm wondering how it work for liquid biopsyes...if the test find both cancer cells with a mutation and without...if they can tell exactly what is going on, or they just see what is going on on the majority of cancer cells...
Biopsies from one tumour have more genetic differences than similarities, finds studyBMJ 2012; 344
doi:(Published 08 March 2012)Taking a single biopsy from just one part of a tumour may fail to provide a full picture of its genetic landscape, indicates the first study to analyse the full genome in different regions of the same tumour, which shows much greater variation in mutations than previously thought.
Two thirds (66-69%) of mutations identified in the study were not shared by different biopsies taken from the same tumour. This may help to explain why using single biopsies to identify biomarkers used to direct treatment with molecular targeted therapies has often proved unsuccessful in improving long term survival from cancer.
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@Amel_83 that's very interesting. Thanks for adding to the thread, although it makes things more confusing! Ha! Good question about blood biopsies though. Maybe it is the majority,as you say, based on Guardants response on my report that maybe the cancer is stable/responding to therapy etc. so there is less available.
That makes me wonder what these treatments do to the mutations, if anything.
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I know it is confusing...I'm already planning on asking 2 or 3 liver biopsy to my MO and I know he is going to think I'm crazy 🤣
I'm also want to do a Guardant test, I don't know what to choose yet…
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@amel_83 let your MO think you are crazy! I am realizing that we have to fight hard for ourselves. And it would be a good experiment for everyone if your results are what you expected. Ask for a few of the liver and a Guardant blood biopsy too! Why not? It's getting by the insurance that will be the tricky part I'm sure.
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Yes I realized too that we have to fight hard to obtain something...for me is been a constant battle...
Fortunately i just found a nice oncologist, hopefully he will listen and take in consideration my opinion as well, and answer my questions.
They will pay the biopsis, but not the guatdant test unfortunately. But if it is less than 500 I will pay it myself, i think it is too important!
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I had the Tempus test. My insurance turned down payment for it, but Tempus never billed me, and I was told they would never charge an individual patient more than $100. It's pretty outrageous that insurance won't cover a test for such crucial information.
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Is not much the insurance, that unfortunately i don't have, but the oncologists that doesn't prescribe it...
Here (Italy), they only test for the very few "famous" mutations (Her2 status, pik3ca, er/pr status, esr1). That's all I hade done in the hospital. Plus a liquid biopsy I had to pay myself i think about 2 years ago...but now I feel like i need another one at next progression. It is passed long time since and plus i want to know more than just few mutations.
I think is very important, especially after reading here so many intetesting and useful things.
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@amel_83 That makes a lot of sense and I would want the same thing!
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I had a situation with Guardant. Right after the blood was taken for the biopsy, I got a letter from Guardant asking for the Explanation of Benefits when my insurance eventually rejected payment for the test. This was even before there were any results. I called my insurance and they said I was covered 100%. So I let it go. Then I was getting letters from Guardant wanting me to sign something that gave them access to my medical records so they could appeal the rejected payment. Nope. Not giving them that. So I called my insurance and they said that they just needed the doctor to get "prior authorization" for the test. It's a bunch of papers the doctors have to fill out justifying the test. Simple as that. I called the doctor and gave them the information and I called Guardant and gave them that information. I had to do this at least twice with each. I continued to get letters from Guardant asking for permission to have my medical records to appeal the rejected payment. I had to call them back and tell them AGAIN what was going on. @tougholdcrow I would call your insurance before hand and ask what is covered. Maybe it was something simple that happened with your insurance too.
Interestingly enough, a few days after my newest Guardant testing, I got the same letter from Guardant asking for the EOB again when my insurance rejects the payment. They must get denied payment for a lot of insurance companies based on the form letter I get each time.
@amel_83 do you know the name of the liquid biopsy you had? And do they only test for the few common mutations? Are you going to have the liver biopsies soon? Good for you for trying to find more treatments for yourself. If you are paying for it anyway, why does the doctor have to prescribe it? I think it's only fair that you find ALL the possible treatments.
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@dulcea wow crazy, I wonder if Guardant don't need personal medical files for their own purpose maybe. I know many companies look for medical informations for their studies and researches. I was contacted by a company called BioMassive that offer free search for clinical studies in exchange of the access of personal medical records...also they are probably payed from whoever make the study I believe.
I had tissue biopsy in liver and bones , with a "basic" results at my hospital (the very few mutations that I wrote before). This is payed by the public ealth care system. The liver biopsy maybe was not done well, as no cancer cells was collected. The bone biopsy come out with no mutations at all.
I had a liquid biopsy payed by myself when my oncologist denied me a biopsy, just after the first line of therapy for metastasis. Because at the time I didn't had any biopsies other than the one made on my primary cancer back in 2018 (and the liver one that come out with no results)! So I decided to do it myself and pay for it. It actually saved me from Docetaxel, in favour of Capecitabine, as I had a very hig TYMP, so I'm actually happy I spent those money.
So basically the MO prescribe blood and tissue biopsy with just basic results (er status, her2, etc...), but if you want a more complete test with many mutations you need to pay it yourself.
(The liquid biopsy I choosed was a proteomic test called OncoOmixDX and a genomic test from a company called Eurofins Genoma Group based in Italy. Not sure if they are the best but I was in total panic and I choosed the first one I found in a total rush! I wasn't agree on Docetaxel as my second line of therapy immediately after ribociclib+letrozole. Also on the later bone biopsy it came out i was still 98% estrogen positive! So why Docetaxel!)
Oh and about my next liver biopsy, I hope is not going to happen soon as I'm only in my third cycle of Eve+Exe, but allthough the first two months my liver enzime dropped down a little and one was stable, in my last blood test my ALT went from 40 to 90...scarry! So I want to be ready if this mean that my current treatment is already failing…
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@amel_83 you are smart to plan ahead for what might be next. I feel the same way. I'd like to avoid chemotherapy as long as possible!
I am unfamiliar with estrogen related to docetaxol so I'll have to look into that too!
I keep saying "Wow" to you but you have really done well in taking care of yourself when it comes to MBC! I worry about the folks who don't have the money or the sense to do so.
Initially I had a liver biopsy and then a Guardant blood biopsy. The liver biopsy just showed the kind of cancer (breast, ER/PR etc.). I got a second opinion a few months later and that doctor suggested I also have the liver tissue tested since "alterations are not always seen on ctDNA" (blood biopsies). The liver tissue testing turned up an ESR1 mutation. So clearly, they did not test for mutations initially on the liver. WHY NOT?? I wonder if this is typical. Wouldn't it make sense to do so?
All of this supports the reasons for more than one type of biopsy and more than one sampling of the tumor itself.
I hope your liver biopsy is not in the near future either!
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Yes me too, what i learned here is to delay chemo as long as possible, and to exaust ER before jumping in to Docetaxel. It is also what an USA doctor told me, doc. Hope Rugo. She is really good.
I also think about all the people that can't pay for treatments and tests...and the one the trust the oncologists too much without a second opinion. Not everybody can or are able to get informed, and is not a fault! And especially here in Italy most older people dont read english, and most studies and publications are in English. And even if we have free ealth care, it is not always good! (In fact I'm burning all my disability pension on second opinions, hospital trips and test!).
I actually learn to get more informed the hard way myself: i went to get check out my breast when i discovered a minuscular hard sead like node in my breast, I was sure it was cancer, hard, attached, doubled in size in 10 days...but the oncologist told me it wasn't cancer for sure, not to worry even if it grew, to come back in three months. Back than i had no doctor experience, never been in an hospital, i thought doctors knew everything, especially more than me! Silly me... I was wrong...when i went back i guess it was too late. Now i don't trust no one, and always ask so many different opinions, and than decide myself. But i know is too late now for me, I can only tell all my friends and family to be carefull and ask second opinions, look for informations...and maybe i will save somebody else...
It is interesting that they didn't test for esr1 on your first liver biopsy...i really don't understand why they don't just test for everythings. It is good that you were able to find it out! Also i didn't know that alterations are not always seen on blood biopsy...so i will ask the guardant on the liver as well if it is possibile. I thought by now they were able to make them accurate. Thank you for pointing that out!
I'm learning so many things here!
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Amel, I'm also impressed by how you advocate for your health, keep it up, girl, you are a rockstar!
I've learned that mutations like ESR1, even if it isn't detected in blood, can still exist and be detectable in tissue biopsy. now I understand why my MO didn't order mutation testing on my first liver tissue biopsy, because it was already detected in the blood, so he focused on HER2 and hormone status. good to know!
here is the link to search for clinical trails, and since you are a great researcher, I'm sure you will find something promising.
honestly, I didn't know why my MO ordered the liquid biopsy through Guardant and the liver tissue biopsy through Caris, so I did some research and found out these well-known genomic testing institutes:
- Guardant Health: specializes in liquid biopsy tests for advanced cancer.
- Foundation Medicine: genomic profiling to identify targeted therapies for cancer patients.
- Caris Life Sciences: molecular profiling services to help guide cancer treatment decisions.
- Genomic Health (now part of Exact Sciences): Oncotype DX test for breast cancer.
- Invitae: genetic testing for a wide range of hereditary conditions, including cancer.
- Tempus: uses artificial intelligence to analyze clinical and molecular data to provide insights into cancer treatment.
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Snow-drop thank you!
And thank you for the useful information!
It is interesting your test history, your MO seem well informed
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I finally was able to secure an appointment with my second opinion doctor. I love her. She actually answers my questions, unlike my local MO.
To summarize: I had a liver biopsy which picked up Pik3 and ESR1 mutations along with a few unhelpful ones. The 1st Guardant test I had picked up all the same except for the ESR1. The 2nd Guardant test picked up nothing at all, not any mutations at all. The oncologist stated that the test just did not pick up any cancer cells. Simple as that. Why not? That's where the question lies. She said once you have the Pik3 and ESR1 mutations, you always have them. She said even the Pik 3 would have been found in my initial tumor. So is that Guardant failed or is it because there is less cancer circulating right now due to treatment?
I also wanted to have another liver biopsy based on what @amel_83 stated about having more than one tumor biopsied. She declined that request stating that usually the only thing that might change is the hormone receptors (usually only negative to positive) and the HER2 status. I wonder if everyone agrees with this statement. Something else to look into.
We also made treatment plans for my future based on my next PET scan and if/when/how it shows progression. She is getting in touch with another doctor who has had success in a trial with people who have failed Pik3ca treatments (I am currently on Truqap). They have just confirmed the toxicity level so are going into the next phase of the trial. Of course she couldn't remember the medication name but emailed the doctor and will get back to me to add to my future treatments. I would probably need a liver biopsy prior to that to determine hormone and HER2 status.
@snow-drop thanks for that link for the trials. I had never come across that one before. I have spent a lot of time on that!
I hope everyone is doing well.
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@dulcea it would be nice that the guardant test didn't pick up any mutations because there were not enough cancer cells circulating! It happened to me that a liver biopsy didn't pick up anything, and it was because didn't pick up any cancer cells at all.
I will try to ask for two biopsies and see what my MO say. Even if only er status and her2 can change, may be important for therapy decision.
I'm happy you found a nice doctor that listen at you! Also planning ahead and see what options and trials are available it is smart!
Unfortunately my onco, which is very informed, never have enough time for me, so he dosen't realky look in to my situation or talk about the future until something bad happen...this really freack me out.
I actually learned here in the discussion "clinical trial" about the VELA trial, with blu-222 and I may do that soon (my AST went so high, so I'm afraid is going to be very soon...if i don't get a liver failure before). They already took me out of my meds until next blood test because of that…scarry!
About the guardant test, my MO told me that if i really insist I can do it (i need to pay more than 1000 euros out of my pocket for it, soo much!), but in his opinion it is useless. He say that only the more common mutations (the ones that they already test at the hospital for free, like her2, esr1, er status, pi3k...) actually have a correspondent med, so every other mutations are kind of unhelpful...he say maybe i can find a med approved for a different pathology that cover an eventual rare mutation, but it is not prooved that testing for more mutations rise your chance of having a better response.
So between thecost and what he say I'm now indecided...
I will like to ear other people opinion about this...
Anyways good luck, and if you find out, let us know the name of the medicine the doctor was thinking about!
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@amel_83 yes, I am very glad to have this second opinion doctor. When I see her at an appointment (hard to get!) she knows my whole story inside and out. I have to correct my local MO often about my history of cancer/medication etc. She does not read up on me prior to seeing her and I see her once per month. Yikes.
I was also reading about the blu-222 trial.
So the high AST was from the meds and not from progression? I guess not having progression in your liver is good but having issues with your liver due to meds is not helpful. Can they reduce your dose?
Yes, that is a hard decision you have about testing for more mutations. Is there one company that tests for rare mutations?
I'm with you wanting to put off chemo for as long as possible. I'm not ready for that.
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Your new onco sound really nice and smart, lucky you!
Unfortunately they don't know why my AST went so high, I'm afraid for liver recurrence. But they had to stop my meds because my MO say it is dangerous to keep taking meds with my liver so messed up...
I will have new blood test result in about a week and a TC scan at the end of the month.
As regarding the test I was thinking about Guardant, or another similar from an Italian lab, but prices are very similar, and mutations are probably the same. Just I trust Guardant more because ot is more widely use.
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