Signatera test -pros cons
I have seen discussion on here about this test, But my oncologist has never mentioned it.
Looking for information you have received from your doctors on pros & cons of test.
Thanks.
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Yes, there have been a few discussions on this topic recently. I am not a medical professional and was dx’ed over a decade ago. I have gotten lazy and not kept up with newer tx. After recent progression, I am learning about this too. We have had a few members, not widespread, use this test. My understanding is that it may lead to treatment by targeted therapy but I am still not understanding what this means because what are you targeting? Traditionally, metastasis has been defined as your original tumor moving beyond the breast to other organs and those specific organs are the target. This thinking did not extend to circulating cells which had not set up shop yet. Additionally, not all oncologists even used the more traditional circulating tumor cell tests anyway.
Here is an easy to read article which sheds some light but I think these tests still have some ways to go in terms of what actions could be taken on non-specific metastasis. The words targeted therapy are throwing me off when there is no known target .
Sorry but I still can’t copy/paste URL’s on bco. Please google the following from ASCO Daily News:
Balancing the Benefits and Harms of ctDNA Surveillance in Early-Stage Breast CancerApril 3, 2024
Lajos Pusztai, MD, DPhil, FASCO, and Mariya Rozenblit, MD
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thank you. I haven’t seen a lot of discussion on the boards about it- so it must not be used a lot, at this time.
I will ask my MO about it at my next appt in a couple months.0 -
ann5631,
I recently had Signatera ctDNA done.
It first came up in discussion with my MO after my BCI results last year. I had finished 5 yrs of AI. BCI showed high risk for recurrence with no benefit to continue. My MO told me some patients insisted on Signatera testing for reassurance. She told me that the SOC for early breast cancer after completion of AI is yearly visits with bloodwork and imaging only if symptoms. I didn’t really push for Signatera test.
Had my yearly visit last month and MO brought up Signatera test again. I didn’t feel like she was pushing me to have it done. Just as a way to do follow me more closely because of high risk for recurrence. She said she would do aggressive imaging if the test came back positive. She told me she is following 15 patients this way and 1 has had a positive test. Imaging showed a lesion in femur.
The thing that I want to discuss with her before the next test is what would happen if test came back positive but nothing showed on imaging. I think it relates to what exbrnxgrl is talking about. I think there are clinical trials studying this very thing. If there isn’t definite scientific info about the course of treatment, I’m not sure my MO would treat me at that point. She is a very SOC oncologist. I’m ok with that bc I trust her.
So, what do we do with that info for the above scenario? That’s what worries me.
I guess the one benefit of doing Signatera testing is that maybe you find the metastasis in organ earlier than waiting for symptoms? I don’t know…I think I’ll send my MO a message in portal before the next test (can’t remember if it’s done every 3 or 6 mos). Depending on her answer, I’ll make a decision if I’m going to continue with the tests.
Is there a specific reason you want to have the test? Are you high risk for recurrence? I do realize we are all different and can have different reasons for wanting the test done.Here are my stats…
I had ER+PR+HER2 neg IDC, 3 positive nodes and LVI.
BMX, chemo and rads.1 -
exbrnxgrl,
Thanks for posting that article. I just read it. Helps clarify things for me.
The things that bother me about the test are addressed in that article. Lots to discuss with my MO. I wasn’t prepared when she brought it up at my yearly visit. Thought we had left that behind at the previous visit when we discussed BCI results so I didn’t do any more research.
My MO is always open for discussing things. She always answers my questions and I think she is on top of the latest trials and research.
Again, thanks for the post.0 -
This is all very new and interesting to me. I see my onc on Wednesday and was planning to ask him about the particulars of the test. I'm going to try and read the article Exbrnxgrl offered ahead of time. Thanks to all for your thoughts about all of this.
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https://outcomes4me.com/webinar/us
Sorry that I can’t make the link live. This is a very short piece with video. It keeps taking me back to the part I don’t really understand. That is, if your test is positive, what action can be taken? At present, it seems very unclear. Yes, I suppose imaging could be a follow up, but if nothing is seen on imaging then what can be done? How does one know what drugs might nip progression in the bud when there is no evidence of progression save for the liquid biopsy?
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My MO made a comment last year when she first brought up the test. She said some patients wanted it done for reassurance. Her concern was what to do with info if it was positive. She said the science isn’t there to treat. This was last year. I want to discuss this same topic with her before my next test.
I looked into a trial that does a bone marrow biopsy looking for cells. If positive then there are 3 arms of treatment. Didn’t pan out for me to join the trial. My understanding (after listening to a podcast on this site) is that this is where science is at…trying to stop ctDNA cells from forming tumor at distant sites. However, there is not a treatment that is SOC for it yet.1 -
There are curently clinical trials addressing prevention of recurrence before biopsy evidence of metastasis.
PALAVY (the one mentioned by @dimples90) is researching the possibility of eliminating ER+ breast cancer cells if found in a bone marrow biopsy. My MO was in favor of this approach but I was not eligible since I can't take one of the three treatments being tested to eliminate the cells if found. So far this looks promising according to those running the trial.
TRAK-ER is using ER+ ctDNA results which are positive to see if two years of treatment with palbociclib and fulvestrant for those with a positive ctDNA test will prevent metastasis. NCT05625087 is similar but uses alpelisib. Another trial, ZEST, using niraparib was ended since it didn't have promising results.
There are other trials with the same aim for triple negative patients.
For those who are stage 4 there are programs using liquid biopsies to try to decide when to switch treatment like MSK-ACCESS at Memorial Sloan Kettering NYC,
None of this is SOC but the research is in the pipeline. My MO still would not treat based on ctDNA since there is no certainty metastasis will happen and no way of evaluating the effectiveness of a treatment.
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This trial sounds interesting, but it's unfortunate that it would take a bone marrow biopsy to get the information needed. An NP at my clinic told me bone biopsies were pretty horrific to go through, and I had heard that before too - long before I ever had cancer. Do they ever try to do things without pain and minimize side effects, etc? I hear about new possibilities and then of course they always come with some awful side effect profile. It makes me wonder if they even have that aspect of things on their radar at all.
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Hello @ann5631. This is a great question. In addition to others sharing their input, here are a few resources on monitoring and surveillance that you may find helpful.
Tumor marker tests:Â
Some doctors use marker test results as early indicators of breast cancer progression (the cancer getting worse) or recurrence. They may use this information to make decisions about when to change therapies — if current treatment does not appear to be working — or to start treatment for recurrence. If you have an elevated marker, your doctor may check that marker periodically to assess your response to chemotherapy or other treatments.
About ctDNA (circulating tumor DNA) tests, to search for molecular presence:
For early-stage breast cancer, the aim of these tests is to detect, and treat, cancer cells before they develop into a full-blown recurrence, thereby improving prognosis.
Personalized tests (based on original tumor sample): Signatera, Invitae, PersonalisÂ
Tumor-naive tests (no tumor sample required): Guardant RevealÂ
 Signatera ctDNA personalized tests measure the presence of Minimal Residual Disease (well in advance before it can become picked up in scans). Signatera requires the original tumor sample.Â
Currently, Signatera will offer financial assistance to cover the cost of their testing, should your health insurance provider deny coverage.
Not all oncologists agree with offering ctDNA testing because there is no standard of care procedure established (at this time) if a positive test were to result in the absence of positive scans.
https://dailynews.ascopubs.org/do/balancing-benefits-and-harms-ctdna-surveillance-early-stage-breast-cancer
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I’ve had a bone marrow biopsy and while it’s not as easy as a blood draw it was OK. Conscious sedation was given but I knew what was going on. They would have put me under more if I wasn’t tolerating it. There is a small possibility of infection and some discomfort afterwards. As a comparison I’d put it at the yuck factor of a root canal.
The measure of success in all this is no metastasis/slowed progression which does not require another biopsy.
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What I don't understand is if a patient with a positive Singnatara test is given treatment, how do they measure whether the treatment works? Is there not a danger of using treatment too soon and because of that using up treatment too quickly or have I got this all wrong?
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This sounds very promising, especially the clinical trials. I can’t wait to see if this yields any specific treatment results or recommendations because I am, under the current circumstances, not seeing the value of it…yet!
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@sunnidays, Your statement summarizes why my MO would not treat with a positive Signatera test result. This might change in the future but that's why they run clinical trials.
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threetree,
Bone biopsies, are for most people, easy and painless as the drugs are great! Now, a bone marrow biopsy might be different and seems more invasive but I am not familiar with them. But if you ever need a straight bone biopsy, most folks have an easy time of it (thanks to Versed!).
I don’t think drugs are ever developed with the intention of delivering pain and side effects. The reality is that most drugs that treat cancer and its symptoms are very, very powerful drugs that along with, hopefully, improving one’s condition or even eliminating it, effect many other systems/functions of the body. This is not great but is current reality and for many people, not all, the side effects are temporary. I think we all fervently wish that there were drugs strong enough to kill our cancer with no side effects but that is not what we have. I am not a scientist or doctor and I don’t believe that researchers are ignoring the things you point out, but their focus is on cancer killing and there are simply no benign and gentle treatments that have equaled the efficacy of currently available drugs. I’ll be first in line when they find those gentle drugs.1 -
Exbrnxgrl - I had a bone biopsy with the Versed, etc., and it wasn't particularly pleasant, but certainly could have been worse. Also, a couple of weeks after that biopsy on a spinal vertebrae, the vertebrae collapsed/fractured and I have chronic pain there now, so in the end it was not a real quick and painless thing. I've heard that a marrow biopsy is different and not easy, but I have no experience with that personally, nor do I know anyone who has and has told me about it. I agree that researchers aren't trying to give us drugs with bad side effects, but sometimes I just don't think side effects weigh very heavily in their scheme of things. I like to bring it up and think that some of us should from time to time, to keep that issue out there. I get the feeling that if we all just "take it" and are satisfied merely with our cancer being slowed down (not that that isn't a really big deal in itself), that there is less motivation among researchers to do what they can about side effects. I think all of us are very appreciative of strides that have been made, and the fact that we can do much better than people who've gone before us, and we do accept the side effects as something that comes along with all of that, but again, I just wish there would be more focus on reducing/eliminating them when new and various treatments are researched and developed. Like you, I'm no doctor, scientist, or researcher, but from what I've experienced side effects and the fear and anxiety that come anticipating a lot of these procedures, just aren't high on the list of priorities.
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Not being a scientist nor medical researcher, I can only speculate so please take these as totally unqualified observations 😉. I feel as if from the very beginnings of treatment research, the primary focus is on fixing the problem and that’s where it largely remains though we can clearly see that attention is being paid to se’s because they have improved in many cases. Still, if a side effect is thought to be temporary but the tx does its disease slowing/killing job, it’s thought to be worth dealing with se’s to reap the benefits.
Of course, I too hope to see more research done into drugs that don’t come loaded with so many se’s.0 -
I saw my oncologist on Wednesday and asked him about the Signatera test and the issue presented here about whether to treat or not, if there are circulating cells but no apparent mass that has formed. He said the issue is controversial in oncology itself and that different people have different opinions. He said that the test actually is a good one and that he uses it for various things, and that it is especially good for colorectal cancer. He said that then it does also have some good implications for breast cancer in certain situations. I couldn't follow everything he told me as it was "beyond me" and very medically technical, but the basic gist that I got was that yes, Signatera can identify circulating cells that indicate metastases even when there is no solid mass, or anything that shows on imaging, but that that alone would not be the deciding factor about whether to treat or not. He suggested that there are many other factors that would be looked at before deciding that treating a "non mass" stage 4 cancer was warranted or not. He indicated that the Signatera tests alone would not be the deciding factor. He said that certain cancers, and say different types of breast cancer that can present in different ways could be treated as stage 4 without anything showing on imaging. If a certain type of cancer is at issue and the Signatera test comes back positive, all the factors involved (history of the cancer, it's progression, location, type, etc.) might point to a good outcome with treatment, but not always. He said that in some situations some cancers can spread without forming any real mass that shows on imaging, yet it can be widespread, and he gave the example of tumors that can metastasize to the lining of the abdomen. He also said something about carcinomatosis, which is related. He said that when those kinds of cases are presumed, treating based on Signatera results, but nothing on an image, can be warranted. It made me think of what we all hear about tumor markers and how they can increase, but not be enough on their own, to assume that cancer is spreading and change treatment. The doctors need imaging back up and more information, with the tumor marker levels just being one factor in the whole assessment. My onc seemed to suggest that it's the same for the Signatera test, i.e. the results of the test are just one factor that is weighed among many, and that sometimes it can justifiably lead to treatment of stage 4 when nothing on imaging supports the suspicion of metastases. (Sorry for the ramble and likely redundancy. As I said, I didn't quite get it all myself, but hope this helps in some way.)
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threetree,
Thank you for giving us your doctors explanation. Because the usefulness of this test with respect to bc is still not clear, the explanation was couched in a lot of tentative language, which screams for further research (which is happening). Are there MO’s who view Signatera results as actionable for bc? Yes, quite likely as medicine is not a cut and dried science and bc can be so variable but for the present, I think most MO’s move to imaging as the next step after a positive Signatera. I see so much potential good in this but for bc, more research, in terms of what action can be taken, needs to be done.
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I will share my recent Signatera testing experience: I was diagnosed with stage IV in June 2024. One bone met in sternum and possible mass (never biopsied) in soft tissue behind sternum tumor. I had 4 courses of HP protocol and anastrozole starting end of July 2024. In September 2024 I had another PET/CT scan and was NED. I chose to take a "treatment holiday" for three months. My MO then suggested I start Signatera testing. I had my first Signatera test 3 weeks after NED PET. Signatera test was negative. Six weeks later I had another Signatera test which indicated extremely low positive. Four weeks later had another PET/CT. This one showed slight uptake behind sternum. We initiated HP and anastrozole again in January 2025. I had another Signatera test in January 2025 before starting treatment again. This test was again extremely low positive. My MO suggested having Signatera tests following each PET to see if the scan and ctDNA results align. I just had another PET/CT the end of March. It indicated a reduction in the soft tissue uptake, but some uptake in the sternum spot again. I got another Signatera test when I went in for my HP infusions the following week. It showed strong positive. Apparently, I do track well with the Signatera test. So, basically, I will now get the Signatera test every 12 weeks or so, following my PET/CTs.
In addition, I get CA15-3 and CA27.29 tests every 3 weeks. They have remained in the normal range since July. Both were slightly elevated when I was first diagnosed. It seems that my tumor markers do trend somewhat, but the ctDNA test seems more reliable, in my case anyway.
I am now having 5 courses of RADs to the sternum and soft tissue. Already completed 2; 3 more this week. We will then wait 12 weeks following radiation to do another PET/CT. That much wait time is recommended following radiation because there may be an inflammatory response and, of course, inflammation can raise SUVs, giving false information. Following the PET/CT, I will do another Signatera test. Really hoping for a negative on that one, which would be indicative that everything is gone, especially if it corresponds to the PET/CT findings.
My MO feels ctDNA tests are an added piece of information, but does not rely solely on them. That being said, once I finish my 5 courses of radiation to the sternum due to the new uptake in that area and, if I return to NED on PETs, but the Signatera test after the PET indicates positive, there will be the concern as to where the new metastasis might be, given I just had a clear PET. That is where the conundrum exists. It will be interesting to see if my PETs and Signatera tests continue to align or not.
Hugs to all, Pam 💗
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livinglifenow,
Thanks for your perspective on the Signatera test. My medical center does not use it nor tumor markers. While I understand that tumor markers are not reliable for some, and that is why many MO’s do not use them, I am still hung up on the lack of action available if the Signatera test is positive. That is, perhaps, my own hang up. Conundrum is an excellent word for a positive Signatera test.
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@exbrnxgrl I do agree with a lot of what you say. I believe Natura, the company that does the Signatera test, is being very generous on their costs to patients if their insurance does not cover the test, because they are trying to gather more information to get FDA approval to become a standard of care test. Still very much in the early stages to determine what to do if results are positive but images show nothing! So far, in my case, I seem to track. But not everyone does and that can cause unwarranted stress. Like you've said, How do you treat for something when you don't know where it is and exactly what the particulars are?
Hope you are feeling better and recovering from your radiation treatment.
Hugs, Pam 💗
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As a stage 2B with very high risk of recurrency, who has been on AI for seven years and counting, I am following this thread with interest.
My MO at a national cancer center never mentioned this test. She didn't recommend the breast cancer index either. I suspect the reason is the same. She has no evidence-based treatments to recommend in case of a "high risk with no benefit from further AI" result in the BCI test. And my guess is that she has no evidence-base treatements to recomment in case of a positive Signatera test, either. But I will ask in my next check up.
I am getting scans as part of the regular 7 year post-diagnosis check up and they are already causing me enough stress for no discernible benefit.
So I share the perspective ("hang up") of @exbrnxgrl 🙂
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@laughinggull Each of our BC journeys is so very different. We have to trust our MOs to lead us down the right path, but also question them regarding any new information we have gathered. I can't imagine "knowing it all" when it comes to cancer!
Sending hugs your way for clear scans!
Best, Pam 💗
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