Routine marker testing and recurrence... worth it?

[Barbara2]

Is there benefit in finding mets early? He told me right from the start (at diagnosis) that when mets are found, treatment will follow, but finding them early does not increase the time of survival. That really puzzled me; it didn't make sence. I wondered, what if a person lets mets go on and on, untreated, then what? Wouldn't you die earlier if the mets were not treated? It would seem so, unless none of the treatments were of benefit to you.

I asked him again the last time I saw him...what is the thought behind finding and treating mets early? He said it is controversial. Some oncs believe finding them earlier is better; that the tumor burden is smaller and easier to manage. He agrees with that logic; that finding it earlier could lead to a longer survival time.

We have read, though, remarks from many people who have posted here, that their oncs do not believe in doing markers. They wait until symptoms show up, then run tests.

I think some of us feel the most comfortable when we believe we are being as aggressive as possible with our with our cancer; that by finding it early, we will benefit. I guess each of us knows what we have to do to cope; and if we feel better using markers, and our oncs agree to letting us do so, then we are more at peace. Everyone has to do their own thing when determining how they can best handle this disease.

Below I have pasted some remarks from Dr. Pegram, that relate to this topic.

Tumor Markers

What is your opinion of having markers done?
I do them. They’re not very good, but I do them once in a while. It’s about like the barometric pressure. “How’s the weather today?” Oh its 760 millimeters of mercury today; well that’s one atmosphere, so that tells you maybe it’s not high or low but it doesn’t tell you the temp, clouds, precip. So that’s exactly the analogy I would make of the tumor markers. They’re a piece of a puzzle; by themselves they’re virtually worthless. But I still give them.

Do positive or negative hormones make a difference?
<O

It doesn’t matter. I tend to dismiss the subset analysis because the numbers get so small that you can’t really interpret them.
<O

In regards to a health maintenance program when considering scans; how often to do them? Brain scans?

We don’t do any. I wouldn’t do any. Unnecessary radiation exposure. Just get a history, a physical examination and some blood work and that’s it, unless you have symptoms or an abnormal blood test.
<O

What about the brain?

Same thing. If you don’t have any symptoms you shouldn’t need a brain scan.



I (Barb) prefer at least a yearly brain scan.<O

[dlaxague]

StephN said: OK - here is where I had trouble with the study Marcia posted and the NCCN's guidelines NOT meshing. The study is from 1999 and the referenced guidelines are from 2000.

Debbie now: The study about tumor markers said that markers were useful in detecting mets before symptoms. Which they are - no dispute. But other studies have shown that there is no benefit to doing that, and that's what the guidelines are based on. Mets detected by symptoms respond just as well to treatment as those detected before symptoms, say the studies, and the NCCN. QOL is also equal in the two groups, per the NCCN studies (which I think are updated as of 2007). There is no way to know if this is true on an individual basis. You can't say that because you had your mets detected with TM's, and did well, that it was TM's that made the difference. You can think that, and are perfectly entitled to do so, but you cannot prove it. No more than someone who didn't do well can blame their situation on the TM's or lack of them. These kinds of things only show up in large groups, not in individuals, and when well-done large studies show significant results, that's considered proof. For an example near to our hearts (hah, no pun intended, but it happened anyway), herceptin for adjuvant treatment did not happen until large studies were able to show its benefit. When we allow emotion and anecdote to rule, we risk getting into trouble and doing harm, as happened with the bone marrow transplant fiasco. Have you read the book just out about that? False Hope, by Richard Rettig. I haven't but am eager to do so.

See, I have a problem with rambling. Back to the issue at hand: are there subgroups for whom this follow-up recommendation is not true, as several have insisted? We don't know, but I can't really think of a reason why that would be true. For treatment - yes there are definitely subgroups that respond differently, many of which we probably don't even know about yet. But this basic primary follow-up question seems more likely to have one answer.

Something not much mentioned in this discussion except by a few individuals who experienced it is the cost to QOL in anxiety related to close surveilance, and also to false positives that result in even more testing.

(Wouldn't it be interesting to know how long, on average, it would take a tumor marker-detected met to produce symptoms - probably not that long, which could be why there's no difference - or it could be that response is response, and has not much to do with bulk. That often seems to be the case).

Alaska Angel, now I see why that's your name (smile). It's good talk to you again. Thanks for staying level-headed and kind.

As to translating to laymen's language, that's always hard. But both the abstract's conclusion and the NCCN guidelines are pretty understandable and don't need translation. I'll quote them and see if you don't agree:

The study that begins this thread sums up their results: " 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)."

And the NCCN guidelines, one short paragraph (I remember now trying to do this before here, and formatting gets all messed up - sorry):

Interval history and physical exam every 4-6 mo
for 5 y, then every 12 mo
Mammogram every 12 mo (and 6-12 mo post-RT
if breast conserved) (category 2B)
Women on tamoxifen: annual gynecologic
assessment every 12 mo if uterus present
Women on an aromatase inhibitor or who
experience ovarian failure secondary to
treatment should have monitoring of bone health
Assess and encourage adherence to adjuvant

hormonal therapy.

Enough,
Debbie

[AlaskaAngel]

Hi Deb,

I am not sure I understand entirely....

I think the guidelines are based on a large group of people who have bc, most of whom will never benefit from markers because most would never recur. So if the idea here is that most folks with bc do not benefit from having markers in particular done, then you would get a much smaller bah humbug out of me (although you might still get one).

And the last I heard, HER2 still isn't shown as being a defined risk factor in Adjuvant, etc. But since the greatest risk for reccurrence with HER2's initially is in the first 2 years (and I don't think that is true for the broader group of all bc), since there is no guideline that is based on studies for HER2s alone, wouldn't it make sense to use markers for HER2's for the first 2 years at least?

A.A.

[dlaxague]

Hi Alaska Angel,

I'd take this offlist as I don't think many are still interested, but I can't seem to find how to do that. I also can't figure out how to make this conversational, with your words and mine clearly differentiated. I've put >> before your words, and nothing before mine.

>>I think the guidelines are based on a large group of people who have bc, most of whom will never benefit from markers because most would never recur.

So, a semi-humbug from you? Laughing! I don't think it has anything to do with those who don't recur. The studies upon which the guidelines are based address those who do recur, and they find no difference between those whose recurrence is detected by scans/markers or by symptoms. I'm beginning to feel broken record-ish.

>>>And the last I heard, HER2 still isn't shown as being a defined risk factor in Adjuvant, etc.

I haven't been to "Adjuvant!" for awhile, but there used to be a discussion about HER2 and you could add to the risk by going to "prognostic factors", I think, and put whatever you thought HER2 increased the risk by, although I think there was some suggestion that it was by less than 2-fold. But now with adjuvant Herceptin, that's a moot point. (those of us who did not get Herceptin will never know what the increase to risk was for us, I guess - although - maybe it WILL be in Adjuvant, when the benefit of adjuvant Herceptin is shown - showing up as as opposed to no Herceptin, like he does for the various chemos, vs none - hmmm). Anyway, I assume he's waiting for more survival stats for Herceptin's adjuvant use, but that's just a guess. Who goes to SABCS? Peter Ravdin's pretty advocate-friendly, we could ask him when he'll put HER2 in Adjuvant!.

>>But since the greatest risk for reccurrence with HER2's initially is in the first 2 years (and I don't think that is true for the broader group of all bc), since there is no guideline that is based on studies for HER2s alone, wouldn't it make sense to use markers for HER2's for the first 2 years at least?

Well, hmm. I don't think it's just HER2 that has higher, earlier risk, although you're right it's not ALL bc. I think that basal/triple-negative is as early/high as HER2, if not more-so now with Herceptin in the picture for adjuvant HER2+. And any ERPR negative tends to recur earlier (although again, those graphs are from pre adjuvant herceptin days). It fascinates me to look at these graphs of recurrence timing but what I've noticed is that they tend to stratify by only one detail - ERPR, or HER2, or triple negative - but rarely by, say both ERPR and HER2.

And again, if the principal holds, I don't know why it would be any different for an early vs. late recurrence. Scans/markers improve outcome, or they don't - regardless of when the recurrence happens. Or maybe not. In fact, it could be argued that earlier recurrences are more likely to be faster-growing (more aggressive) and so the interval between being able to pick them up with scans/markers, before symptoms might be quite short. If that's true (and I'm only speculating that it might be), then IF scan/marker detection made a difference, you'd have to be doing them pretty darn often to benefit from that difference.

I notice that there are two meaning to "early" mets. "Early", as when relatively small and/or not causing symptoms. Or "early" as in within the first few years. No point to that noticing - just an observation of one place we might misunderstand ourselves.

This has been a fascinating, though sometimes painful, discussion. I'm wondering how many on this list, post-adjuvant primary treatment, did use scans or markers as part of their routine (asymptomatic) follow up. I did not, except once and that was without my knowledge/understanding.

Debbie Laxague

[AlaskaAngel]

I have to admit, my last entry wasn't my best!

My personal interest in this is broader, though, than the narrow focus that comes with accepting rough guidelines in the attempt to be entirely objective in how to best deal with the disease. The discussion ended up being limited to considering only what benefits there are in terms of lengthening survival. Perhaps because I am able to see that the guidelines are so rough, I don't see them as being terribly objectively important. For example, if you know by way of markers that the disease has returned, even if you happen not to gain longer survival, and you have limited resources, you will have more choices about how to spend them in what time is left, rather than finding out late in the game. As we both could see from the discussion, some want to know and some don't, without either being "right" or "wrong". But it does matter that markers can offer some people the right to know. It can offer them the right to decide on making a change in treatment as well -- and for some that might mean starting Herceptin that they have never had, or doing Taxol because of the recent knowledge that it works much better for a certain group. It can mean deciding to STOP treatment, if one feels QOL would provide more benefit, where without the markers one might have been more inclined to continue suffering treatment that wasn't working, all the time wasting resources that aren't helping.

So I'm not sure the points about being "unemotional" and "factual" and "evidence-based" in applying what are only rough guidelines in the first place is actually all that meaningful.

With all the false trails we have been herded toward (those HER2's who were put on tamoxifen when it was deadly for them, those who should have gotten Taxol and didn't, those who were given Adriamycin when it wasn't helpful due to TOPO II, the resulting leukemias, and any further mutations caused by the carcinogenic chemos, etc., etc., the question about the effectiveness of treatment is still open. Is doing markers ineffective, in prolonging survival, or was the treatment ineffective regardless of markers or no markers?

AlaskaAngel

[Becky]

I am always into a lively discussion and I am rather late in the game here.

As far as markers are concerned, although they may not work for everybody, they do work 69% of the time (at least that number was reported somewhere in this thread). This is a non invasive, radiation free way of knowing that something is going on. I am not a simple person but I am a very logical person so... I do think that finding mets as early as possible is good for a number of reasons. First, the tumor(s) would be smaller. To me, it would seem that cleaning a pan with just alittle burned on food is easier than a pan with a ton of encrustation. Likewise, stepping on a bug is easier than killing a lion. One liver met can be radio abalated and then get Herceptin (lets say). A fully loaded liver needs a lot of guns. Also, a fully loaded liver can be causing life threatening symptoms. Some tumors, in the wrong location, can be cutting off the blood supply to the liver causing portions to die (and all the toxic reactions that occur because of tissue death). Symptoms are there for a reason and in the case of mets, none of those reasons are good. It is not like the flu where the symptoms are actually the result of your body fighting off the bug and winning. Symptoms from mets are the result of your body losing.

When it comes to the brain, I think early detection is even more important. You can try less invasive treatments (Tykerb, certain chemos, gamma or cyber knife) before doing WBR (of which you usually can only do once). I feel very strongly about the brain because the brain is who you are.

Just as detecting cancer as early as possible is important for the first go around, it is just as important in the second go around imho. Before tumors are so big or abundant that they start shedding to even more locations - including the brain!

As Stage 2A I got baseline CTs, bone scan and a year out, a brain MRI. Now we know what's there and if I should need scans again because of markers or symptoms, if something new is there, it probably isn't good news. But I do markers. Are they a little scary? Yes they are. Once mine went from 11 to 21. In time, I learned that is my "flip flop" window with my numbers always going up and down in that window. Do I get anxious? Yes - I just had another breast lump that was analyzed to death and was determined a cyst (which by that time the lump was already gone). I found it during my monthly breast exam. Do I get scared to do the monthly? YES, YES, YES but I DO them. Cancer and its vigiliante aftermath is scary. Very, very scary so we must be brave and sometimes in my case - you have to pretend to be brave and do all the brave things - (what I mean by this is if I waited just 9 days for my lump, it would have disappeared on its own). And if you don't want to know, I suppose that's fine. But do you want to live? I think most do so you should want to know so sometimes, you have to walk into an even darker and scarier place - the time where you wait... wait for the marker result, wait for the scan result, wait the days until the scheduled mammogram. Time is not our friend and time is also our best friend (2 years out NED, 5 years out NED). Fear is not our friend but fear is also our best friend (get that lump checked, don't let it go....).

In all, bc survivors (and regardless of our individual status - we are all survivors) are a unique bunch. You all are the best bunch. We are all dressed up to go to the beautiful party of life everyday but underneath our gowns, we are wearing bullet proof vests!

Party on!