cfDNA and monitoring response to MBC treatment

zarovka
zarovka Member Posts: 3,607
edited July 2018 in Stage IV/Metastatic Breast Cancer ONLY

The weak diagnostic tools we have are one of the biggest challenging in managing MBC. Tumor markers accurate for some people some of the time. In my case they have been a inverse measure .... they have risen only when my tumor burden was actively decreasing but I know that at some point an increase in tumor burden could cause them to increase . okay, I understand what is going on and why .... but what do I do with that information. Small changes in scans can be equally misleading and need to be corroborated by a second scan, in my opinion. But I don't want to delay changing treatments if things are not working. I also don't want to get scanned frequently.

My dis-satisfaction with diagnostic tools has led me to look at diagnostic tools being researched. The consequences of a wrong decision to change treatment or a late decision to change treatment can be as bad as any mis-step we might make in this minefield.

Circulating tumor cells (CTC) are an interesting source of genetic information when you can find them but there are many many false negatives ... people with active cancer and no circulating tumor cells. I don't have any CTC's but I can't say that means my cancer is dormant.

The most promising advance in MBC diagnostics right now, I think, is Cell Free DNA or cfDNA. cfDNA is the DNA from dead cancer cells in the blood stream.
In the US we have been mostly looking at cfDNA as a way to characterize the genetics of your tumors but the change in cfDNA burden ... how much DNA from dead cells you have in your blood ... turns out to be highly sensitive to how well you are responding to treatment.

I would like to start a discussion on cfDNA as a diagnostic tool. I am also wondering if anyone is having this test done in the US or is in trials that monitor cfDNA. I will have it done one way or the other, but at the moment the only place I know I can get the test done is Australia. Sending my blood across the Pacific for analysis will cost about $600. Not super expensive, but eventually the test will be common here. I am sure it is done in the US, but I don't know where.

This article is an interesting survey of cancer biomarkers. The discussion of cfDNA is at the very end.

Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers

>Z<

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Comments

  • Kiss77
    Kiss77 Member Posts: 162
    edited July 2017

    Hi

    I had this test done 3 years ago, in Brussels. It predicted my progressions very well - a month before the rising in TM and positive scan for progression. But no one will change current treatment only because of this test as it is very new. Also they can say which mutation is problematic for the current progression. I don't know what else to say - if you have questions - ask me.

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  • ShetlandPony
    ShetlandPony Member Posts: 4,924
    edited July 2017

    Very interesting. Following.

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  • Midwest_Laura
    Midwest_Laura Member Posts: 168
    edited July 2017

    Thanks for bring this up, Z. I don't have anything to add, but I'll be following thisas well.

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  • zarovka
    zarovka Member Posts: 3,607
    edited July 2017

    Kiss - It is very interesting to hear about your experience. Everything I have read suggests cfDNA is very accurate. I'll keep posting as I research and pursue this test.

    Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer

    CT and Circulating Biomarkers for Tumor Monitoring

    We compared the performance of circulating biomarkers with CT scans in 20 patients with measurable disease (as defined by RECIST21) and for whom circulating biomarker data were available at 3 or more time points over a period of more than 100 days of follow-up. Circulating tumor DNA was detected and showed serial changes in 19 of 20 women (95%) with fluctuations in circulating tumor DNA generally correlating with treatment responses seen on imaging (Figure 4A

    ...

    women with high levels of CA 15-3 had fluctuations corresponding to responses on imaging but with a smaller dynamic range (Figure 4A and 4B) than cfDNA. In patients with levels of CA 15-3 of 50 U or less per milliliter (8 of 19 patients [42%]), no consistent serial changes in CA 15-3 levels were seen (Figure 4C).

    Progressive disease was documented on CT (as defined by RECIST) in 19 of 20 women during the follow-up period; CA 15-3 data were available for 18 of these women (95%). Increases in circulating tumor DNA levels reflected progressive disease in 17 of the 19 women (89%). In these women, on average, circulating tumor DNA levels increased by a factor of 505 (range, 2 to 4457) from the nadir before the establishment of progressive disease.

    CA 15-3 levels increased in 9 of 18 women (50%). In 10 of the 19 patients (53%), levels of circulating tumor DNA increased at one or more consecutive time points, on average 5 months (range, 2 to 9) before the establishment of progressive disease by means of imaging (Figure 4D). In 2 women (Patients 9 and 22), increasing levels of circulating tumor DNA did not reflect the presence of progressive disease as assessed on CT.

    This article is interesting for people trying to understand their CA 15-3 results. For women like me with a CA15-3 of less that 50 U/ml, increases in CA15-3 did not correlate with progression. For women with CA 15-3 greater than 50U/ml, increases in CA15-3 did predict progression.

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  • Kiss77
    Kiss77 Member Posts: 162
    edited July 2017

    One more thing to add: The doc who manages all the things around that test in my country said It is not reliable for bone and brain mets. The first test is done on material from the surgery/biopsy. In this step they determinate problematic mutations. The follow-up is via blood tests. Every 3 months. The good number is 0 for all mutations, but even if it keeps last value it is good thing. If it starts rising even for one mutation - there is big chance to see progression in one, two or even in 8 months. I don't make that test anymore as it is paid now and the price is very....impressive.

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  • zarovka
    zarovka Member Posts: 3,607
    edited July 2017

    Kiss - thank you for these details. Still trying to figure out if and how I can get it here in the US.

    >Z<

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  • zarovka
    zarovka Member Posts: 3,607
    edited August 2017

    I've decided to use this thread to report on my quest for better blood biomarkers for cancer, generally. I think it is a huge problem that we have to wait until we have a tumor the size of a pea, or see changes in size greater than a cm in scans to know we have progression. That's a lot of cancer cells ...

    I got my Biocept circulating tumor cell results back today. I had my first Biocept test done about 4 months ago. At that time, they found no CTC's. This time they found one, which doesn't sound too bad but bursts my fantasy that the cancer is completely dormant. The problem is that it is cytokeratin negative. A little bit of googling suggests that it is a cancer stem cell. Cytokeratin negative CTC's are associated with a negative prognosis.

    Any knowledge or experience out there?

    >Z<

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  • zarovka
    zarovka Member Posts: 3,607
    edited August 2017

    I just got Foundation One ACT back ... came back with "No Genomic Alterations Identified" at the top but there was one Variant of Unknown Significance... GNAS F124fs*556

    I was really looking for the burden, or amount of cfDNA in the sample. Hoping to use it as a biomarker ... increasingly done outside the US. Calling to find out whether they can report the burden.

    Anyone have the Foundation One ACT done? How are you interpreting and using the results?

    >Z<

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  • vancouverdeb
    vancouverdeb Member Posts: 37
    edited August 2017

    My CA 15-3 markers are consistently below 50 & I wish there were a more meaningful indication as to how I'm responding to treatment - nothing to add but that I'm finding this really interesting and following....

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  • ABeautifulSunset
    ABeautifulSunset Member Posts: 990
    edited August 2017

    z- I had Foundation One testing. Came back with nothing of any value that I could interpret. I think unless you have a significant identifiable mutation, it's pretty useless...except to tell you that you have no significant identifiable mutation. I guess that's something.

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  • Lumpie
    Lumpie Member Posts: 1,650
    edited August 2017

    zarovka, I am fascinated that you have had these tests done. This is a distinct area of interest for me. I have begged both my primary MO and second opinion MO to let me do this type of test. They have declined. At one point I contacted Pathway Genomics to see if they would give me the name of any doctors offering the test. They declined. I just went to their website. They have taken down info on the Cancer Intercept product. I have not done an exhaustive search but my impression from a bit of web research is that the FDA may have forced the company to take the product off the market. (sigh) If you have tips on how to get these, please share!

    At the time of my original diagnosis, I searched for clinical trials for a cfDNA product in hopes that I might be able to participate. None were accepting participants at the time. I work in a field where the use of these tests is routine (maternal infant health). They are widely used and very reliable for that purpose. I have no doubt that they hold tremendous promise for cancer monitoring and for "personalizing" treatment. Many of us would jump a the chance to sign up for a clinical trial. It's very discouraging that they are not available. I hear the public health people talking about efficiencies, cost-effectiveness, the need for proven protocols and not "over-treating" cancer. But the fact remains... their well established protocols have failed me repeatedly. It's hard to imagine that modern medicine, even with its current limitations, can't do better than this. I suppose we need more research, more advocacy. Maybe if I end up on leave from work and am still doing ok, that is where I will spend my time and energy.

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  • zarovka
    zarovka Member Posts: 3,607
    edited August 2017

    I've been on the phone with Foundation One this week and they won't report cfDNA burden even as "research data" to my doctor ... who ordered it for that purpose. Will talk to him tomorrow. Not very happy to have blown my opportunity for blood based testing on this Foundation test which provided me nothing I was looking for and found not genetic mutation to boot.

    The FDA did shut down the cancer intercept cfDNA test from Pathway as not sufficiently supported. I have no idea exactly what that test was, and whether they deserved to be shut down or not, but the really need to get on with the research in this area. We do have a serious problem over treating cancer because we don't have sensitive and accurate tests for its presence. Scans really are not very sensitive.

    Lumpie nice to meet you. You are a bit ahead of me on all this topic technically and I hope that you keep chiming in on this thread.

    >Z<

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  • momallthetime
    momallthetime Member Posts: 1,575
    edited September 2017

    Zar super interesting thread, what a dream this would be.

    I could give you these facts, I don't understand it all very well. Dani had F1 done just a few weeks ago.(2nd time in 2 1/2 yrs. first time from the illiac and this time from the liver biopsy). It says she has a high TM, so can you explain to me what could that mean? I get that it's not good, but what else would we need to know?

    Also, it says she has about 19 mutations – some have clinical trials, some don't. Also, interestingly they mention a lot of tx that she was on and it had not helped her, but it still says that it's recommended to her type of mutation, but it did not. Will all that, Onco still is at loss, what gives??

    Re: I got to a navigator that works with F1, he sent me a whole study of what trials are good for her mutations, etc…

    Re: 15.3 has been rising, slowly but surely. And the way the scans came back, it showed some progression of new lesions, some lesions got larger. Some are stable. Her BT's are not gr8 this time either. Another BT that I think they could see how things are going is the LDH, that has been going up a lot, so I could see that things are not so good.

    With all that, they insist she should continue on the trial of DS8201a, I really don't think it's doing much for her.

    She also had Guardant360 done about 1 yr ago, this Onco does not think much of it. It's done with a blood test, and she did not respect it much. Interestingly, she had a few mutations on that one, but it did not show the same on F1 that was done now. Maybe one or two.

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  • thrivingmama
    thrivingmama Member Posts: 136
    edited July 2018

    Hi all - It looks like this thread has been quiet for a while, but I'm curious what people's experience continues to be with this type of testing. I recently had the Guardant360 (cfDNA) test done. It showed .2% of one of my mutations. Interestingly it didn't pick up a couple of the other mutations that they say they test for, despite the fact that I know I have them (from Caris and FoundationOne testing). And I don't know what to make of the .2% number other than I must have active tumor somewhere in my body, despite showing as NED on PET/CT. My plan is to reorder the Guardant360 test to track the % over time. Has anyone used Guardant360? Over time to track?

    I also saw a naturopathic doctor yesterday. She wants me to do the Biocept test. She said the advantage of that test (aside from being FDA approved and insurance approved, supposedly) is that it will test for cancer stem cells. >Z< you mentioned having a couple of the Biocept tests done, so I am curious if you found them useful/accurate?

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