Finally!!!!! a paper showing which tumor markers (and serum her2ECD test) are best at

[Lani]

discovering recurrence early, determining if treatment worked/working and with specificity statistics even. And stats subtype specific, even! Most oncologists do not want to use CEA, CA and serum her2 as they say "they don't mean anything" or "we don't know what they mean" or "they can bounce all around and not reflect what the cancer is doing and can also miss a recurrence"

Although the sensitivity of each test individually are in the 32-50% percent range, the combination of all 3 performed in the group in which these are most accurate (the her2+ group...yeah!) is around 67% and waiting for a recurrence to become macroscopic and measurable to start a new regime can let the tumor bulk up so much of it is anaerobic, unavailable to the blood supply so the new treatment can't get to it, and allows many different additional mutations to develop/clones to take over so the next treatment will have a harder time keeping it under control.

Let's spread word about this one as my guess is they are going to need larger studies, multiinstititional etc before guidelines and practice are changed. NICE may decide 60-60% isn't cost effective, etc. This is where, in my opinion, advocates can be helpful as they can "get in the face" of those who determine the guidelines and remind them that some flesh and blood humans personally have something at stake here.

Let's get those larger studies done quickly and...if they pan out...work to get the guidelines changed. It seems the group where determining if utilizing these markers and changing treatment, adding additional early imaging may make a difference will be most clear and beneficial will be....the her2+ group.

The serum her2 ECD test is going off patent. Don't know if that means that it will be more widely done or performed more cheaply
(when was the last time you remember a test being done more cheaply?) but perhaps we can get its use to be more widespread.

Now an oncologist will probably say that since the sensitivity is only 50-60% why should they change treatment if the tests are positive? I bet they could get stats regarding if the tests are positive two or three times in a row over an x week period the specificity/sensitivity goes way up with each time it stays that way and similarly, having elevating tumor markers should be a reason to retest whether that means PET/CT, CTCs, CHEST CT, BRAIN MRI, abdominal MRI or bone scan. These tests have been shown NOT to be cost effective when done when the patient is first diagnosed, but would be when tumor markers are rising IF catching the recurrence, biopsying the recurrence and changing treatment early make a difference in overall outcome. It seems intuitive that it would, but oncologists/bean counters won't change their approach until a large multiyear study demonstrates number they can quote. It seems to me those numbers will be easiest to get with her2+ bc as there are now a large number of treatments proving effective in contrast to her2= breast cancers.

As regards the sensitivity, here too, serum her2 ECD should excel in her2+ bc patients.

This has been one of my rare opinion posts. Usually I just post information.

Anyone else want to chime in?

Here it is:

Clin Chem Lab Med. 2013 Feb 13:1-9. doi: 10.1515/cclm-2012-0488. [Epub ahead of print]
Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer.
Pedersen AC, Sørensen PD, Jacobsen EH, Madsen JS, Brandslund I.
Abstract
Abstract Background: The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer. Methods: Serial serum values of CA 15-3, CEA and HER2 were determined in 107 patients with recurrence after breast cancer. Fifteen of the patients had primary disseminated disease, nine patients only developed local recurrence during the follow-up period and the remaining 83 developed distant metastases. Results: In the group of patients with distant metastatic disease (n=83), elevated serum levels of CA 15-3 (>32.4 U/mL), CEA (>2.5 µg/L for non-smokers and >10 µg/L for smokers) and HER2 (>15 µg/L) were found in 49.4%, 38.6% and 32.5%, respectively, at the time of diagnosis of recurrence. CA 15-3 was significantly better than HER2 (p=0.027). The most sensitive combination was obtained using CA 15-3/CEA (60.2%) or CA 15-3/HER2 (57.8%). Combining all three tumour markers raised the sensitivity to 63.9%. In the subgroup of patients with tissue HER2+ tumours, the sensitivity of HER2 increased to 55.6%. The best combination in this group was CEA/HER2 (66.7%). In the subgroup of patients with tissue HER2- tumours, CA 15-3 was significantly better. The best combination was CA 15-3/HER2 or CA 15-3/CEA with a sensitivity of 55.8% and 59.6%, respectively. Conclusions: The combination of several tumour markers enhances the sensitivity for detection of metastatic breast cancer. We recommend HER2 or the combination of CEA and HER2 in tissue HER2+ and CA 15-3 or the combination of CA 15-3 and CEA in tissue HER2-.
PMID: 23403727

[Lani]

PS

I have been hoping to get a researcher interested in validating the serum her2 ECD test in CSF in order to follow how IT herceptin treatment is working, determine the optimal dosage and administration and combinations etc.

If anyone with leptomeningeal mets under treatment has a doctor who might be interested in this, please let me know. The tests kits for about 28 patients will cost $1000 and before the test begins they will need some samples of CSF from patients without brain mets (ie from a researcher working on something else or a clinician who has to draw CSF to do myelograms, rule out MS etc) to be sure there is no problem using the test on CSF in general. Here too advocacy could help push a project along which might help those brave volunteers like Courtney who just tried the dosage/administration schedule that had been done in a handful of cases before. Perhaps we might also find that we could diagnose her2+ brain mets as well as lm mets early if lumbar punctures are performed before symptoms occur in those at high risk, as we know that catching brain mets early when they are small and few DOES make a difference with allowing SRS to be performed rather than WBR.

[CarolineC]

Lani,

Once again I thank you for your information which has helped me immensely during my years of treatment.

A few months after I finished my initial protocol, in early 2011, I persisted with my onc to run TMs. I was already having symptoms (of a sternal met which I didn't know about) after finishing my Herceptin and continuing with Tamoxifen and a few months later my CEA had doubled but still within the range of normal. My onc said he wasn't concerned and I said "if you're not worried, I'm not worried" but I should have asked to run them again in another month. By the fall of 2011 I had been having alot of pain and a bonescan (which my onc wouldn't order but my gp did) and further CT scan revealed a 3cm lesion right through my sternum and my TMs were out of normal range-NOW the oncs were looking at them. I was stunned and angry that I had been saying something was wrong and had been dismissed (this was now the third time I said something was wrong and it was)

I kept track of my TMs after having rads, then restarting Herceptin and starting Letrozole and after chemo and they came down.Now my CEA has been rising again and I wonder (and hope) that it is because of a possible infection.

I know for some people TMs are not effective, but I also wonder if patients are being told by their oncs that everything is "normal" when in fact there may be an upward trend. I have had problems WITHIN the range of normal. This whole experience has changed me into a person I never used to be; I now ask for all test results and question any changes and have become my own advocate and I watch my numbers.

I also have the great debate with my oncs that things need to change for metastatic patients-I think it is just as important as in early stage to find problems early and treat them. My local onc said "what would that do?" and I replied "buy me time" and with all the treatments that are coming out I believe in my heart that metastatic patients should have monitoring and that it DOES make a difference.

Oncologists need to recognize that TMs can be very effective and I think these tests should be protocol. I am from an area that sticks to protocol alot and everything needs to be evidence-based-I have been in awe of Courtenay, Brenda and Sheila's wonderful medical teams because they tried things that were outside of the box.

I hope to see a shift in the way Stage IV patients are treated; we need to feel like we matter. I will be printing out this new information and will ask to have the Her2 test as well, but I'm bracing myself for the great debate again.

[Nancy L]

Every breast cancer patient has heard of Dr. Susan Love but many may not know she is also now a cancer patient---not breast cancer but her current treatment for leukemia has changed her attitude about research and how cancer patients should be treated. This is a recent interview she did on this subject
http://articles.latimes.com/2013/feb...ancer-20130213

I wouldn't wish breast cancer on anyone but if oncologists could walk in the shoes of a metastatic breast cancer patient, I know things would change for the better.

Lani, perhaps Dr. Love's foundation would be interested in helping with research on tumor markers.