Routine marker testing and recurrence... worth it?

[Soccermom]

I am hoping that Lani will have a look at this and comment. I was just looking at my original pathology and came across this article online. Its from 1999 and I wonder IF it still holds water,so to speak?...

<TABLE width="75%" border=1><TBODY><TR><TD width="35%">C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients.
Molina R, Jo J, Filella X, Zanon G, Farrus B, Munoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, Estape J, Ballesta AM.
Laboratory of Biochemistry (Unit for Cancer Research), Hospital Clinic, School of Medicine, Barcelona, Spain.
</TD><TD width="65%">Anticancer Res 1999 Jul-Aug;19(4A):2551-5 Abstract quote
C-erbB-2, CEA and CA 15.3 serial serum determinations were performed in 250 patients (follow-up: 1-4 years, mean 2.5 years) with primary breast cancer and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). Ninety-five patients developed metastases during follow-up.
RESULTS: Abnormal c-erbB-2, CEA and CA 15.3 serum levels (> 20 U/ml, > 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis were found in 28.4%, 31.6% and 46.3% of the 95 patients with recurrence, with a lead time of 4.2 +/- 2.4, 5.0 +/- 2.5 and 4.6 +/- 2.7 months, respectively. One of the tumor markers was the first sign of recurrence in 69.5% of the patients. Tumor marker specificity was 100% with levels lower than the cut-point in all 155 patients without recurrence. Tumor marker sensitivity was clearly related to the site of recurrence, with the lowest sensitivity found in locoregional relapse and the highest in patients with liver or bone metastases. C-erbB-2 sensitivity in early diagnosis was significantly higher in patients with c-erbB-2 overexpression in tissue (10/12, 83.3%) than in those without overexpression (1/34, 2.9%) (p = 0.0001). Likewise, higher levels of both, c-erbB-2 and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse and a higher lead time were found in PgR+ patients (CA 15.3) or in PgR- patients (C-erbB-2) (p < 0.015).
In conclusion, tumor markers are useful tools for the early diagnosis of metastases, being the first sign of recurrence in 69.5% of patients with relapse (76.3% in patients with metastases).
</TD></TR></TBODY></TABLE>

Marcia

[hutchibk]

All I can offer is that my CA 15.3 has always been the earliest indication that I had distant mets... in 05 when I showed up with my first recurrance, lungs and chest nodes, CA 15.3 had started to slowly rise a couple of months before we did scans. Then in 06 when it showed up again in chest nodes and bone spot in neck, CA 15.3 had started to inch up again before we did scans... and again in April 07 when we found the brain mets, CA 15.3 had started to inch up yet again from the plateau number that it had been steady at for 8 months, before we did the brain MRI. So for me, TMs are definitely worth it!

[Carolyns]

I have had them run for 19 years since the first of 3 times with BC. At age 32 with my diagnosis I demanded continued follow up beyond 5 years. I figured if they were mandated in the trial...why not continue? Each time I went for more than 5 years with NED. Recently (the past 7 years) my insurance company no longer allowed my onc. to do the blood draw. I had to go through my primary and then he was to send results to the oncologist. Well evidently when my markers started to rise no one noticed. So even in this case my markers would have given us the heads up that something was up.

So, I believe that markers are a good thing to follow and were in my case. I would add to that that it is a good idea to confirm that no news is good news on any test. Had I asked about my markers then I would have known that they were on the rise and I could have pushed for more testing earlier.

Good luck, Carolyn

[fullofbeans]

Great question thank you I had just been wondering how much to untrust the Ca15-3.

Could someone explain why there is a distinctinction between why is Pr+ is (Ca 15-3) and Pr- (C-erbB-2)? not quite sure what they mean by that.

Also what about the CA125?

Thanks in advance for info

[Faith in Him]

I unfortunately will not be getting any TMs. My onc doesn't trust them. But after reading all these posts, I wonder if I should push harder.

I am kind of confused, because they do draw blood about every other herceptin infusion. I wonder what they are looking at?

[hutchibk]

I know that some/many docs don't believe in them... I am glad that my doc does. He doesn't rely soley on them, but they are an integral piece to the puzzle in my journey - and like I said, they have always been the earliest indication of my recurrances. Especially before I was metastatic, and being Her2+, he felt that it was important to have as much screening info as we could in case I developed mets (we wanted to know as early as possible)... and my rising tumor marker was our first red flag to look at things when we found my first mets, and ever since then, mine have corellated directly to recurrance. Mind you, my doc always reminds me that the TMs might not always rise even if I have new activity, or that them rising may not always mean new activity, that we can't count on them being absolute every time, but they are a big part of our puzzle.

[new shoes]

I am getting my first TMs drawn next week. What kind of numbers should I be looking for? What is considered low, moderate, or high?

[StephN]

Hi Beans -
The CA 125 is to detect Ovarian cancer. I have had this drawn with no opposition from my med onc. Once we have ONE cancer, we are at HIGHER risk for a second cancer to come along. Reproductive cancers are high on that list. So, I consider that I at least have a base line for the 125 with two tests reading at the same level.
One thing I am not sure of is whether Ovarian is normally more hormone driven.

As for the BC markers and CEA, they have always been good indicators for me. Before we really knew that to be the case, my med onc explained he wanted to keep checking them as the favorite places for BC mets were more sensitive to the markers (as stated in the research cited by Marcia) and with my more aggressive disease profile he wanted to keep me close on his radar screen.

The CEA marker was sensitive to my brain mets and CA27-29 rose and fell with my extensive liver mets.

In short, if the onc is aware of how best to use the markers and what they are best at indicating, they might not be so mistrustful. We also have the HER2 serum test, which may not be approved for early stagers, but many of us have put it to good use since its release.

[tousled1]

My oncologist ran tumor marker tests and my HER2 serum every 12 weeks. My TMs never changed - right now it is 15.1 and it was 15.3 when I was initially diagnosed. Therefore it is not a god indicator for me. We have found that the HER2 serum test is much more reliable in my case. It was the first sign that I had developed mets. some oncologists do not run TMs.

[fullofbeans]

Thanks Steph for clarification, I am assuming C-erb2 is the same as her2 serum (?)

My CA15.3 was elevated when I had mets to liver does that mean that I should trust this test when in the future it continues to show no change (I like to assume), because it showed it has worked for you in the past?

what I am asking is that if a TM has worked for you in the past is this an indication that it will work for you in the future?

[StephN]

Hi Beans -
This is from the Revolution Health website:

"cERB2, also known as ERB2 or HER2, is an oncoprotein overexpressed in cancer and is detected by immunohistochemical staining or by fluorescence in situ hybridization, known as FISH, which detects gene amplification. This test is performed at the same time as testing for hormone receptivity, or estrogen and progesterone receptors."

Maybe in other countries they use the cERB2 designation - had not noticed it before you mentioned it.

My cancer center does not use the C15-3 as my med onc explained they feel the CA27-29 is more accurate and a newer test. Anyway, if your marker was elevated and you had mets, then there is no reason NOT to continue to check it periodically. That marker test may not be sensitive to ALL kinds of mets, but if your liver acted up again, seems to me the marker would rise.

I have had my CA27-29 taken either every 3 or 6 weeks for the last five years. It has been in the same range (normal) within maybe 2-3% fluctuation. Since I have also had clean scans to corroborate the marker, I feel good continuing to use markers and drawing a HER2 serum (the Bayer Elisa test) a couple time a year for good measure. Then I go on about my life with peace of mind.

[Soccermom]

Steph, Thanks for stepping in and explaining the cERB,CA-125. Based on the responses I have read here,many still get routine markers. I know the prevailing school of thought is that there is no survival benefit , BUT, its obvious that its helped many get prompt attention when #s are elevated. I find it frustrating that the powers that be would still have no tests be done as followup. Peace of mind can be a powerful thing.
Thank you all Ladies for your thoughts and input!
Marcia

[hutchibk]

I would like to stand as proof otherwise in deference to the prevailing thought of no survival benefit. I would not be here now were it not for tumor markers!

[Mary Anne in TX]

This thread made me remember again, how complex this ol' disease really is. I do the CA 27-29 every time I go for herceptin and find comfort in knowing that something besides my not so good awareness is "watching out for me"! I spent a couple of hours reading again about the marker I get and was reminded of all the other things it can be triggered by. But I do know that when it rises, I get more tests, scans, etc. I can't imagine not having it. My last ones were 30, 41, 35, ?. I'll check on the last one today. I have a tendency to want to "believe that all is well" and it's a good reminder to stay alert! And to keep believing too! Thanks to all who shared. It's like the food and supplement threads. I know what to do, but I like so much to be reminded how and why! It also keeps getting me out the door each morning for my walks! ma

[dlaxague]

Hi all,

There is a big difference between the value of tumor markers for those who have already had a distant recurrence, and those who are NED after primary disease. The article that started this thread was about tumor markers after primary disease, and so replies from those with mets are irrelevant. Interesting, but irrelevant. And did you notice that the article did not address benefit from finding mets sooner with tumor markers - it simply said that it was possible to do so. Duh. But why would we want to do that, if there's no benefit in it?

If one has had that distant recurrence, and tumor markers were elevated (not all cancers elevate tumor markers), then tracking the markers is one tool for monitoring response to treatment. They are usually not stand-alone and are supplemented with scans, but tumor marker results can help signal when it's time to take a look with scans. Most docs use tumor markers as one of the tools to monitor advanced breast cancer (for those whose cancer does elevate the markers), especially when in treatment. For those that achieve NED after mets, it's a little more gray and I don't know of much research there. It could be argued that at that point, it's back to the after-primary-disease algorhythm where there's no benefit to finding progression before symptoms appear. The exception here would be monitoring for brain mets because that is one area where it helps a lot to find them when they are smallest. But that's typically done with scans rather than relying on TM's, right?

So on to that area that's so hard for us to get our minds around -tumor marker and/or scans after primary disease. The recommendations for follow-up are for physical exam/symptom report only. (in addition to mammograms if breasts remain, and uterine exams if uterus remains and on Tamoxifen). The reason that this is the recommendation is that good studies have shown that even if mets is detected before symptoms appear (using scans or tumor markers), there is no benefit to surival, nor to QOL. Women do not live longer, or better, if their cancer is detected before symptoms. In addition, there is really very little reassurance in a negative tumor marker - first of all you do not know if it's accurate for you (many recurrences happen with no elevation in markers), and secondly it only tells you about today and offers no guarantee for next week.

Okay - again - talking now to those who are NED after primary diagnosis - this has nothing to do with those being monitored after metastic recurrence. Why would you want to subject yourself to the anxiety and stirring-up of cancer fears that come with a test that offers NO benefit to you? Why would you want to squander health care dollars for a test that offers no benefit? There is no such thing as "catching mets early". Mets are NOT early, they are advanced disease. If mets happens, they either do or do not respond to any given treatment and response seems to have little to do with amount of disease (except brain mets). Look at the many women on this list who had quite extensive mets, even to vital organs - yet they achieved NED-ness with chemo/herceptin. Others with small areas of mets struggle to get a response, trying many different chemos but experiencing steady progression. When talking recurrence, it's less about size and more about response. (that may be true for primary disease too - but we haven't figured out, yet, how to know that).

So - again - for those who are NED after primary treatment, there is no benefit to "watching really closely", no matter how high your risk of recurrence is. NO BENEFIT. Report any symptom that persists for more than two weeks, and be sure that cancer recurrence is ruled out before garden-variety causes are explored. That's all you can do. Of course, we wish that there were a way to make us safer, by using intensive surveilance. But intensive surveilance does not prevent recurrence and it does not improve survival nor quality of life. In many cases, because of the anxiety testing causes, it detracts from quality of life. I know that it's a hard thing to accept and understand, and that we wish there were more we could do. We can hope that someday there WILL be more, but right now this is the reality. Why not accept it and go seize those moments?

Debbie Laxague

[Soccermom]

Debbie,
Thank you for your easily understood explanation!
I currently have markers every 12 weeks, and scans evry 6 mo.BUT that is about to end as I have reached my 3 years since DX.
I am grateful for each and every day that I "believe" that i am NED. If that time should come where I am worried about a particular ache or pain I will pursue it. I guess its all about where your own comfort zone is. For some (even those NED) occaisional
monitoring via markers brings "peace of mind". I would have to say its worth it to them...and I believe that their QOL is impacted.For others,perhaps the testing stress is too much.
I understand the logic behind the arguments...but... we are not statistics and our cancers are as individual as we are.
Warmly,Marcia

[hutchibk]

HI Debbie - read my posts a A LOT closer. They are NOT irrelevant to the discussion. I beg to differ wholeheartedly. I did not have advanced b/c the first time my TMs hinted to us that I should go for scans. I was (stage 2b) at primary diagnosis, had mastectomy and first-line chemo, and then I was NED for 15 months. Luckily we had established a baseline for my CA 15.3 from the point at the end of my initial chemo and routinely followed my CA 15.3 while I was NED and was expected to stay that way... But my doc doesn't like to take chances, he errs on the side of caution with Her2, and believes that the earlier and smaller the mets are when found, the better the treatment options and outcomes will be... he doesn't rely on TMs as an individual indicator, but he considers them in combination with the whole picture. It is a piece of the puzzle. So then after 15 months of NED, my TMs started to inch up for a couple of months and we scanned out of an abundance of caution and found my very first mets (lungs, chest nodes) after being NED for 15 months. We found them much smaller, much earlier, and much much much more treatable than we would had we not had that initial clue and just waited for symptoms. (Sometimes there are NO symptoms until the mets are very large, making them much harder to treat and offering less options for treatment, i.e. liver mets that are small and eligible for ressection as opposed to liver mets that have taken over the liver and can only rely on chemo for treatment...) In my case, because we found it early, we were able to treat it appropriately, less aggressively, and subsequently less expensively. There can absolutely be a survival benefit, and no-one can tell me otherwise. Sorry.

If your "opinion" is that there is no benefit to watching really closely, then that is your experience. I would be careful telling others that there is absolutely "no benefit to "watching really closely", no matter how high your risk of recurrence is. NO BENEFIT." Or that "intensive surveilance does not prevent recurrence and it does not improve survival nor quality of life" - It did not prevent my recurrence, but it offered me earlier info, more treatment options with better outcomes, and did improve my survival and my quality of life. Hands down.

I take offense to the disdainful and self-righteous tone in your post. Expecially a sentence that simply says: "Duh." There are those of us who have had an entirely different experience than the "absolute certainty" that you profess in your post.

[AlaskaAngel]

Soccermom/marcia: Thanks for starting this interesting conversation!

DLaxague/debbie:
1. Why would the amount of tumor burden at time of taking action in previously NED patients be irrelevant? Are there large and reliable studies that show that to be true?

2. Are you basically saying that because a drug like trastuzumab (plus perhaps additional drugs such as chemo or other) is so successful for so many previously NED in knocking mets to the NED again, that there is no reason to use markers for the smaller number of seemingly NED patients in whom it is unknown that trastuzumab (plus perhaps additional drugs such as chemo or other) is not working?

3. In trying to understand the concept that there is really no benefit to markers in those who are initially NED after treatment, I understand that means there are 3 groups of bc patients: those who have mets at diagnosis, those who stay NED indefinitely, and those who eventually develop mets. And I do understand that what you are saying is based on impartial study results, not on intuitive logic. But since we only know for sure who is in which group in regard to those who have mets right off the bat, why would the covert development of additional tumor burden in seemingly NED patients not be more likely to shorten life sooner? Are the studies really showing not so much that markers don't matter, but rather that treatment is so lousy for those in whom Herceptin (plus or minus other drugs) does not work, that knowing the cancer is back makes no difference?

FOB: Thanks for the question about PR- and PR+ and c-erb-2, as I too was confused by that... and sort of still am... I've not seen c-erb-2 used before to mean serum HER2 measurement.... but guess that is what they mean? Always c-erb-2 has meant only the tissue testing before... from what I've seen, anyway.

A.A.

[Carolyns]

Debbie,

I am speaking from my own personal experience. I did not have mets and I was followed with TMs. Like Brenda, I was being followed after a Stage I diagnosis when my markers began to rise. (This was after my second diagnosis with a new primary BC in the other breast.) Perhaps the fact that the doctor's overlooked the rise in markers wouldn't make me live longer. However once realized and combined with more testing we learned that my C-6 vertebrae was ready to melt away and could cause paralysis from bc mets. So in my case it mattered a great deal as a "piece in the puzzle" to get me help and treatment. Getting treatment in time kept me working full time, riding a bike and living life as an active mother to a 9 year old. A big BENEFIT to me and very cost effective.

As far as how the doctor's know whether or not someone with mets detected early will live longer...I don't know. I am sure that there is some scientific calculation based on others but are those others like me? I am not "typical" in the bc population.

I flash back to my diagnosis at 32 (19 years ago) and conventional wisdom prevented me from getting a mammogram for over 1 year. I was too young according to guidelines back then. They were the doctors and I wasn't. Well I finally found a doctor who would prescribe a mammogram and that is how I was diagnosed. The study I participated in required Chemo and followed by tumor markers to be drawn every 6 months for 5 years...I still wonder why TMs? Anyway, that is where I took my lead. If TMs were required in the study than I wanted to continue with them since they had always held steady for me.

I can read the guidelines all day and all night and so far I have been outside of them. I don't want to be right I just want to stay alive even if it means going against the guidelines. My situation has always been slightly in front of the guidelines but I don't have time to wait for the guidelines to catch up. I can only share my experience. It is what it is.

As a breast cancer survivor, I would not go to a doctor who told me that discovering mets early has no benefit to survival or quality of life. I believe that idea could have contributed to the delay in a mets diagnosis for me. As someone diagnosed with cancer in my early 30s I have learned that I must stay alert. It is what works for me but I know it is not for everyone.

Carolyn

[fullofbeans]

Debbie:
'No benefit from being able to detect cancer recurrence early'.. I would be most grateful if you could let us know how you came to this conclusion.

From my personal experience (yet one more person) it was different. Surely you have heard of new technics that allow to treat tumours that are up to a certain size only (brain, bone). Chemo needs to be broken down by liver so if you wait for it to stop working properly..you will be in for a treat..

However I think that it is difficult to check all stage 1&2 and that the risk from radiation from scans should be weighted against the 60-80% chance of being cured. Irregular TM sounds like a nice compromise from the above paper.

There was no need to restate that it was for primary cancer as oppose to MBC, it was already quite clear from the article.

AA:
Thanks, yep I am still confused about the PR- and its association with TMs too..
Steph I am still not sure that c-Erb2 simply means just Erb2