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All TopicsForum: Stage IV and Metastatic Breast Cancer ONLY → Topic: cfDNA and monitoring response to MBC treatment

Topic: cfDNA and monitoring response to MBC treatment

Forum: Stage IV and Metastatic Breast Cancer ONLY —

A place for those managing the ups & downs of a Stage IV/metastatic breast cancer diagnosis. Please respect that this forum is for Stage IV members only. There is a separate forum For Family and Caregivers of People with a STAGE IV Diagnosis.

Posted on: Jul 14, 2017 06:51PM

zarovka wrote:

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<

PM me if you would like to join a BCO Stage IV FitBit Community. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/17/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jul 14, 2017 08:13PM Kiss77 wrote:

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.

Dx 3/8/2013, ILC, 4cm, Stage IIIA, Grade 2, 5/8 nodes, ER+/PR+, HER2- Chemotherapy 3/21/2013 CEF Surgery 7/1/2013 Lymph node removal: Left, Sentinel, Underarm/Axillary; Mastectomy: Left Chemotherapy 7/21/2013 Taxotere (docetaxel) Radiation Therapy 10/11/2013 Breast, Lymph nodes Hormonal Therapy 10/21/2013 Dx 7/2014, ILC, Stage IV, ER+/PR+, HER2- Targeted Therapy 8/19/2014 Avastin (bevacizumab) Chemotherapy 8/19/2014 Taxol (paclitaxel) Chemotherapy 9/17/2014 Carboplatin (Paraplatin), Navelbine (vinorelbine) Chemotherapy 7/20/2015 Xeloda (capecitabine)
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Jul 14, 2017 08:49PM ShetlandPony wrote:

Very interesting. Following.

2011 Stage I ILC ER+PR+ Her2- 1.5 cm grade 1, ITCs sn. Lumpectomy, radiation, tamoxifen. 2014 Stage IV ILC ER+PR+Her2- grade 2, mets to breast, liver, retroperitoneal nodes. Taxol NEAD. 2015,2016 Ibrance+letrozole. 2017 Faslodex+Afnitor; Xeloda
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Jul 15, 2017 01:25AM Midwest_Laura wrote:

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

Dx 11/25/2016, IDC, Right, 6cm+, Stage IV, metastasized to bone, Grade 2, ER+/PR+, HER2- Chemotherapy 12/22/2016 AC + T (Taxol) Hormonal Therapy 5/3/2017 Femara (letrozole) Targeted Therapy 5/28/2017 Ibrance (palbociclib) Surgery 7/14/2017 Prophylactic ovary removal
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Jul 15, 2017 07:03AM zarovka wrote:

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.

PM me if you would like to join a BCO Stage IV FitBit Community. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/17/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)
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Jul 16, 2017 10:59PM Kiss77 wrote:

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.

Dx 3/8/2013, ILC, 4cm, Stage IIIA, Grade 2, 5/8 nodes, ER+/PR+, HER2- Chemotherapy 3/21/2013 CEF Surgery 7/1/2013 Lymph node removal: Left, Sentinel, Underarm/Axillary; Mastectomy: Left Chemotherapy 7/21/2013 Taxotere (docetaxel) Radiation Therapy 10/11/2013 Breast, Lymph nodes Hormonal Therapy 10/21/2013 Dx 7/2014, ILC, Stage IV, ER+/PR+, HER2- Targeted Therapy 8/19/2014 Avastin (bevacizumab) Chemotherapy 8/19/2014 Taxol (paclitaxel) Chemotherapy 9/17/2014 Carboplatin (Paraplatin), Navelbine (vinorelbine) Chemotherapy 7/20/2015 Xeloda (capecitabine)
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Jul 17, 2017 04:31PM zarovka wrote:

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

>Z<

PM me if you would like to join a BCO Stage IV FitBit Community. Dx 12/28/2015, IDC, Left, 4cm, Stage IV, metastasized to bone/liver, Grade 3, ER+/PR-, HER2- Hormonal Therapy 1/17/2016 Femara (letrozole) Targeted Therapy 2/2/2016 Ibrance (palbociclib)

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