Routine marker testing and recurrence... worth it?

[Margerie]

Well, I read the "Up to Date" article. Their license agreement prevents me from posting the article. They do conclude that there is no quality of life benefit from a more intensive surveillance strategy as compared to regular surveillance (physical exams and mammography) alone. BUT the two hallmark studies they quote were both done in 1994:

Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multi-center randomized controlled trial. The GIVIO Investigators. JAMA 1994; 271:1587.

Rosselli Del Turco, M, Palli, D, Cariddi, A, et al. Intensive diagnostic follow-up after treatment of primary breast cancer. JAMA 1994; 271:1593.

These were the 2 main studies, there were other smaller studies with dates from 1985 to 2005 (one study).

They do note that there was a study on 9,000 bc patients that demonstrated that elevated tumor markers can predict relapse with a lead time of 5-6 months over clinical symptoms. They debated whether or not the 5-6 months notice was a pro or a con. My feeling is the newest treatments can make use of the earliest detection for prolonged survival and QOL. None of these studies focused on Her2+ patients.

[Gina]

Hi, Grace,

We know each other from way back so I take no malice at your comment and I realize that this thread has been a bit heated. I also publically apologize to Debbie for teasing her about being an oncologist. That was way out-of-line, and I am sorry, but I still disagree with her comments completely.

Grace, if you have read my threads at all and even moreso from our private emails, you are aware that I aways suggest that the real time to worry is when the tumor marker numbers "go on a run"--they will start rising exponentially and usually rapidly. Many times I have suggested that moderate fluctuations in the markers are often of little consequence and I have even written somewhere here that I have experienced markers going up during certain treatments to be a good thing as it may indicate solid tumors breaking up, especially when the numbers start eventually to drop back down again rapidly. Also, you know that when I look for signs of progression in myself and others, I do not only consider the tumor markers, but also look at scans and the whole bloodwork picture--when the liver enzymes, GGT, Alk phos, and sometimes even bile are also elevating at the same time as the tumor markers, you can be certain, in most cases of her-2 mediated disease, that something is going on somewhere.

Folks, Her-2 protein is not a mythological creature, but something that is scientifically measurable. We know many things about the her-2 protein...we know when it goes up, TNF-Alpha goes down badly affecting the cells ability to commit apoptosis. We know that the more her-2 there is circulating in the system, the more chance there is for cells to grow uncontrollably and, sadly, in many places.

Grace, I am so sorry that you blame me for your current situation as I never want to say anything that makes this already bad her-2 situation worse in anyone, but folks who read me here would know that I would never under any circumstances advise the high levels of toxic chemo that you and your oncologist decided to use. I have used only Herceptin to control my mets since 1999 and have horrible misgivings about the side effects of many of the drugs being used now and in the past on folks with her-2 mediated disease.

In fact, I remember the specifics of your case quite well and have saved our private e-mails that I just re-read as I keep many her-2 case studies to review and learn from, yours was one of the most intriguing. I would be happy to reprint our discussions here. You wrote to me first in Sept 2006 about my comments on Menendez work and olive oil boosting the power of Herceptin and I told you I would highly recommend it, along with Olive leaf and the regular vitamins and minerals I always recommend. Later, you researched more on the serum her-2 tumor marker and even wrote some of your questions to Dr. Carney and made your own decision to get the serum her-2 checked which first came out to be 16. Clearly, I supported your decision and applauded what all you had to go through to access it. We later discussed Carson's work and I was most impressed at how well you were researching many of the more difficult aspects of this illness and even its future potential treatments. Clearly your background as a professional writer was most useful to you in seeking many perspectives and points of view not merely mine. You made your own decisions as we all do.

However, your case was, in my judgement, quite high risk for recurrence, you were her-2 positive and ER- and PR- as I recall--based only on what you told me in your e-mails, and even though you claim that my proddings about the importance of the tumor markers and emphasis on taking them regularly forced you to take more agressive treatment than you may or may not have needed, it is important to note that you are still here, and have since lived to write your book and actually seem to be doing better than many others who read this site who may not have been quite as lucky to have had access to markers or understood their importance. Like it or not, even you used the tumor marker information and your own research to base some of your decisions on and though I agree tumor markers are not perfect, again, I note that you are still living.

Folks, Her-2 mediated disease is very aggressive and its etiology is poorly understood. I think Grace's case, contrary to her intention, provides an excellent example of how the tumor markers may not only have saved her life, but increased its quality. We forget that she could have just as easily died, as thousands have already, from the "not knowing". Yet, Grace has lived, thank goodness, in part, from being aware at least of her numbers and the possible dangerous situation that they could have put her in.

Grace, quite frankly, I still contend that there was a high probability that you were progressing when the tumor markers were increasing and that had you sat idylly by and taken no action, most likely, you would not be here to rebut me..., but I AM VERY GLAD YOU ARE!!!!....smile...

As for many of the problems and side effects you are now experiencing, most can be managed and are not immediately life-threatening as full-blown her-2 mets would be. If you want to discuss this further, you are welcome to respond below or to e-mail me at home any time.

I personally think it was amazing how even after all you went through, you were still able to achieve your dream--your book. You are a role model for us all.

Keep on keepin' on,
Gina

Dear Gina,

I don't blame you, or anyone else, for my decisions. I take responsibility for my own actions. You didn't prod me to do anything, and I honestly don't see how you got that out of "Gina, Go fly a kite." My oncologist advised against running tumor markers. He's a well respected and caring oncologist who has worked solely, and for many years, with breast cancer patients. In addition, I chose him as my doctor; he wasn't forced on me by an HMO. I should have heeded his advice. I didn't, and I regret it. Nothing whatsoever to do with you. You wrote about the HER2 serum test on this site, and it was from one of your posts that I found out about it. But I certainly don't suggest that you pushed me into doing the test. Not at all.

My flippant reaction to your post on this particular thread was a cumulative response to what I viewed as an excessive, and uncalled for, dumping on Debbie because she has another point of view. I should have stayed out of it, as Debbie is intelligent, knowledgeable, articulate, and capable of responding for herself. So my apologies to both of you for getting into the mix.

With respect to the statement you made in your recent post:

Gina's post: Folks, Her-2 mediated disease is very aggressive and its etiology is poorly understood. I think Grace's case, contrary to her intention, provides an excellent example of how the tumor markers may not only have saved her life, but increased its quality. We forget that she could have just as easily died, as thousands have already, from the "not knowing". Yet, Grace has lived, thank goodness, in part, from being aware at least of her numbers and the possible dangerous situation that they could have put her in.

Gina, the above statement is false. I was scheduled for a year of herceptin before the HER2 serum test and I completed my year as scheduled, this August. I most certainly didn't have a better quality of life. I was anxious all the time, stopped writing for eight months, and spent most of my time reading about BC (how depressing). I also had five unnecessary scans, which only increased my anxiety. If anything, my experience proves Debbie's point (as well as that of my oncologist and the wisdom of the national guidelines on not running tumor markers for early BC patients). It doesn't prove yours.

Again, and for the last time ever, my suggestion, based solely on my experience, to anyone who has Stage 1 BC who may be thinking of requesting tumor markers is this. Don't assume that your markers will be in normal range, and don't expect that if they are in normal range that they'll be low normal. That is, be prepared for numbers you may not like and may not expect. You should ask yourself if you happen to have elevated markers if this knowledge will change your course of treatment. If the answer is no, perhaps you should review your decision to have the markers run.

I've read (and written) too many posts concerning elevated markers to believe that all women with BC can take a rise in markers casually. If knowing that there is a likelihood that you are having a recurrence gives you a sense of security, by all means ask for markers. But if you're at all like me and it will cause you much unhappiness, don't. If, as Margery writes above, markers may indicate a possible recurrence five or six months before symptoms, you should also consider that markers rise in many cases before the recurrence can be viewed on a scan.

So now what do you do? You have elevated markers. You request a full body PET scan, and all is clear. Do your doctors change your treatment based on elevated markers if they are not sure if the elevation represents a recurring cancer or it's the result of an infection, or chemo has pushed your markers up, or you have one of the many other benign conditions that can elevate your markers. It seems to me, you do what I did, you fret and wait. Fourteen months later and my markers are normal, and I still worry although not as much. Obviously, markers, for me, was not the right decision.

But again, I am Stage 1A, Grade 2, great margins, no family history of BC, closer to 70 than 60, and as I see it now, I had no reason to open Pandora's box.

Gina, sorry for flipping you off. I don't blame you for anything, and thank you for the kind words at the end of your post. We are certainly a bunch of strong-minded women, aren't we?

[dlaxague]

Hi all,
I'm feeling worn out by this thread. I do love debate and critical thinking and I would like to continue the discussion but I'm weary of the personal ... searching for a word that isn't emotionally charged ... and not finding it. If you've followed this thread, perhaps you know what I'm weary of.

Some of the defenses of personal views have been - well, defensive. And sometimes also offensive, in the literal meaning of that word, which Websters lists first: 1. "making attack, aggressive".

I'd like to repeat that I did not invent the recommendation of not doing tumor markers for follow up of primary disease.

I do not see any evidence that TM's make more or less sense depending upon the aggressiveness of the cancer. It could be argued that the more aggressive the disease, the shorter the interval between being able to detect it with TM's and it showing up with symptoms - which would make it less likely that the TM's would be run at the point in time where they could make a difference, if they ever DO make a difference.

Part of the reason that the national guidelines on TM's after primary disease do make sense to me is that I'm not a big fan of the whole idea of "small" being synonymous with "early". Whether we're talking primary disease or recurrence, I believe that what happens has more to do with the biology of the cancer and less to do with its bulk (brain excepted - see below). Not that it's entirely one or the other - certainly both have some influence. But I think quality trumps quantity in most cases, at least as long as we're looking to eradicate or slow it using systemic treatment. If the cancer responds to the systemic treatment, it seems to respond equally well whether there is lots of disease or a minimal amount. If its response is sluggish or absent, that again seems less to do with bulk and more to do with biology. It's true that larger tumors can do more damage but it's unusual for them to get to the point of being able to do permanent damage without first announcing their presence with symptoms.

Another point is that the quicker a recurrence or progression is detected and acted upon, the quicker one runs thru the available options. It's a valid argument to say that factor alone could impact length of survival. Some perfectly intelligent and thoughtful women and their providers prefer to move slowly even when there's clear evidence of progression, for this reason.

So brain mets - what a puzzle. If it works to zap relatively small lesions, and sometimes to surgically remove larger ones, why isn't the same true for other organ mets? Maybe it could work but it's considered a better option to treat them with systemic meds (chemo, Herceptin, hormonals), so it's not been offered enough to study? Is that because the mets stay gone better if there's response to systemic treatment? Or because systemic tx is more likely to get more of the too-small-to-see lesions and cells?

I don't know the answers but it's hard not to see the questions. IF we ever were to get to the point of removing or zapping organ mets (besides brain), then the argument for frequent scans and TM's would make more sense to me. But to my knowledge, we are not there (yet?). I'm not saying that it's not being done, but there's scant evidence that it makes a difference. And whether we like it or not, we do need evidence to make changes in practice. Again I reference the bone marrow transplant fiasco, and the book "False Hope" by Richard Rettig (very pricey book, which is why I haven't read it yet).

Regards,
Debbie Laxague

[AlaskaAngel]

The debate has been difficult at times, but the issue is one that is hard to understand. I think it is worthwhile.

I don't know what criteria the people used who created this particular guideline, but it is hard for me to agree that this guideline would provide more help than horror for those who are continuing on difficult, uncomfortable, expensive treatments that they are hoping are keeping them NED throughout the time that markers might have helped them to know that what they were doing wasn't helpful. If I read your argument correctly, these patients are better off kept in the dark based on the judgment of the people designing the guideline (who are not, after all, the ones directly dealing with cancer themselves). This guideline then would be based primarily on extending survival and not at all on QOL, since obviously QOL is worsened in this case by being kept in the dark. It seems like they are somehow measuring the value of hope against the hardships of treatment, and how do they manage to do that with any accuracy?

I also think the perceptions about doing markers would be somewhat different depending on whether the guideline is intended to address the UNreasonableness of doing routine markers for everyone who has had bc -- for example, including those diagnosed at early stage whose labs and all other indicators are wonderful and who have been NED from the getgo -- versus those at the other end of the scale, those who have recurred once and are NED. If the guidelines are meant to say that those who have recurred but are NED don't benefit from routine markers, then we do disagree. The guidelines discourage the routine use of markers, but don't say not to use markers altogether. But what would be the guideline definition of the non-routine use for markers?

A.A.

[dlaxague]

Sorry, AA, I rambled and got off the actual topic, which is follow up after primary breast cancer. The guidelines I've been referencing address only follow up after primary breast cancer. The studies on which the guidelines are based, as Margerie confirmed when she got access to that "uptodate" summary, do claim equal QOL for those not doing TM's as part of primary follow up.

The rest was conversation and thinking-aloud, although as I said, it's a valid conversation and some women and providers prefer that style of management after recurrence, for the reasons that I stated.

I think that the option of using markers for follow up after a distant recurrence is considered standard of care, although not all oncologists use them for all patients, for various reasons (they don't work for that patient, the oncologist prefers scans, etc). And they are not stand-alone. They are used as one piece of the puzzle that would include scans and symptoms.

Debbie

[Lani]

hot off the press is all I will add for now

J Clin Oncol. 2007 Oct 22; [Epub ahead of print]
American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer.

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr.
Yale Cancer Center, Yale University, New Haven, CT; M.D. Anderson Cancer Center, Houston; Texas Oncology PA, Dallas, TX; Memorial Sloan-Kettering Cancer Center, New York, NY; National Cancer Institute, Bethesda, MD; American Society of Clinical Oncology, Alexandria, VA; University of Michigan Medical Center, Ann Arbor, MI.
PURPOSE: To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. METHODS: For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and metaanalyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and CONCLUSIONS: Thirteen categories of breast tumor markers were considered, six of which were new for the guideline. The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Not all applications for these markers were supported, however. The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells.
PMID: 17954709 [PubMed - as supplied by publisher]

[hutchibk]

I spoke with my doctor today about this debate. He stated that it is hotly discussed and controversial among oncologists as well... it seems to me to be broken down into basically two groups: *those clinicians who prefer to follow generalized guidelines and prefer to align their clinical approaches pretty strictly in adherance with studies, and *those clinicians who prefer to use every tool at their disposal to determine what is the earliest indicator for an individual patient and prefer to tailor their clinical approach to each patient as an individual. I asked him his thoughts and 20 years of experience regarding the following three questions, and (in my words, not verbatim) this is the result of our discussion:
1. Is there a significant value to using TMs as a method of surveillance post initial DX and treatment? He uses TMs on every b/c patient. He uses them as a piece of the big picture, and that much of the time they closely correlate to recurrance. He does not shrug them off, even if they don't seem to apply easily to a certain patient. For very many, TMs are a very significant tool, but on the flip side, they do not always yield trustworthy info for every patient. It is true that TMs can be tricky and misleading some of the time, and the rest of the time they can offer tremendous insight. He believes that in innumerable cases they offer tremendously valuable early indication and can contribute substantially to offering better and longer survival, and valuable info regarding treatment options and treatment response. He increasingly finds that studies which seem to discount the value of TMs are often flawed and/or outdated. He would rather use TMs than not. And he is very adept at applying the TM info correctly to each individual patient.
Follow-up question: Should clinical cases where tumor markers have been found to correlate directly to metastatic disease be considered merely "anecdotal" in comparison to the studies of the last 8-10 years? If only one life were saved or extended, that is not "anecdotal." The use of the word "anecdotal" to describe a significant success seems to be merely an attempt to diminish the clinician who might not necessarily agree with or has opposite experience of the studies.
2. Is there a survival benefit to monitoring and attempting to diagnose metastatic disease at it's earliest, rather than waiting for clinical symptoms? Unequivocally, YES. In 20 years, he has seen multitudes of lives positively extended due to the earliest possible DX of mets. When they are smaller and more contained, they are easier to treat, easier to combat and eradicate, and come with less collateral damage and less additional medical complications than if found later when more damage has been done. With the earliest possible DX of mets, treatment options can usually be less invasive, less aggressive, and very often yield the best possible outcome. That speaks multitudes about positive QOL as opposed to the difficulty to QOL that can be caused by more aggressive and more invasive treatment options. His example was "why would you NOT monitor (scans, labs, etc) for bone mets and instead wait for symptoms? How would it NOT be better to DX a hip bone tumor met early and eradicate it, than to wait for a broken hip to tell you that you had a tumor that disintegrated the bone and caused it to break? Then you have a tumor that is bigger and might have broken away and continued to spread. Then you have a problematic and expensive hip repair surgery, which may not even be an option. Then you have a patient who is potentially in a wheelchair for the rest of their life. Then you have tremendous pain issues. Then you have a patient who's overall health, well-being, and well-survival potential is tremendously compromised. And on the flip-side, an early DX of the same hip bone met could avoid most, if not all, of those issues. Of course there is a significant survival benefit to finding it sooner rather than later. (And using me as an example... in my case we were able to use a new and less invasive treatment option as opposed to whole brain radiation, because my mets were found extremely early and very small and had not yet produced symptoms. Had we not found them until they were causing symptoms, I would have faced the much more expensive and more physically difficult probability of targeted rads or WBR... Additionally, we have knocked back the same mediastinal nodes twice now due to the assistance of rising markers and earliest possible detection.)
3. What do you think about the QOL distress that some cancer patients claim is caused by close surveillance? Overwhelmingly in his practice, QOL distress is caused when patients worry that they are not being monitored closely enough. If QOL distress is truly caused by close surveillance, then why even do the initial screening exams? Why go for pap smears or mammograms or colonoscopies or to the dermotologist to begin with?

I just thought this might be valuable to the discussion. Maybe everyone should ask their docs about their thoughts and experiences regarding similar questions...

I feel so very lucky to have the doc that I have. He is a true gem. He practices oncology from the standpoint of the individual and not from the starting point of statistical studies. He is part doctor, part psychologist, part priest and he is a brilliant man.

[Bev]

Hi Brenda,

I like the reply. Easy to understand. I guess my question would be if early stage that has done Herceptin need the same level of surveillance? I guess we don't know yet. We are going thru a learning curve but the stakes are high. BB

[hutchibk]

HI Bev - I think that his (and my) opinion would concur... the stakes are too high to not monitor closely - until we know more about the true efficacy of the targeted agents over time.

[nitewind]

Very interesting conversation! After reading thru I asked my oncologist about the tumor markers. He just shook his head and said, "no", " to many false positives". Now I don't know what to think! I would rather know sooner than later, personally. It makes sense that it would be easier to treat the sooner you catch it. But, my oncologist is a non believer in tumor markers. What's a person to do?
I'll continue to watch this thread, like I said, very interesting.

[Mary Anne in TX]

I wish I had more faith in my ability to "catch those early symtoms", but I'm the one who thought my tumor was shrinking on Adriamycin and Taxotere and they were doubling in size! I have no faith in my ability to "catch" anything! I am so suggestable! I believed they would shrink so I "felt" they were! I don't like waiting to know what the markers are and I don't think they are always "right on", but they are the best I have at the present time. I believe that they will replace them with something really right on some day soon, but til then, I'll hate them for not being more accurate and love them for standing beside my "suggestable" mind!
When I hear you talk about your monthly self-exams, I feel a bit of jealousy for your confidence in doing so. I don't trust myself at all! But I do them. Thanks to all for being willing to share your thoughts, and fight for your beliefs! I think that some of the "strong feelings" are about how responsible we each feel for the "newbies" to this site. We so want to help to "save" a sister!
Well, enough for now. I sure do love you guys and thank you for being exactly who each of you are...strong willed, hard-headed, determined to stop ol BC in it's tracks! Believing in the victory, mary anne

[fullofbeans]

Brenda, I wish I had your oncologist! I especially endorse his view about the usefulness of finding mets early.

Regarding the TM use, well this thread started with the actual statistics 69% & 76% which is pretty good. So if your onco says it has too many false well..this is the actual percentage.

However if you are a stage 1 or 2 and do not wish to worry yourself with these then it is your choice, there is no wrong or right answer as to how to handle your eveday life/anxiety post treatment and you know what? you have 70% or so to not need it! That said even if I was stage 1 or 2 I still would have TM because 30% risk or so he in my book worth considering. For me now it is the contrary seeing my TM low makes me smiles and lift me up..it does not stop worrying about symptomatic issues but I know that it helps me stay more cool.

[hutchibk]

Just to be extra clear... my onc agrees that TMs don't always offer trustworthy info for every patient. But then much of the time, along with other monitoring methods that create the big picture, they do correlate directly to recurrances. If he were to not use them at all simply because they are not 100% accurate for every patient, then he would be shortchanging the half of his patients for whom they might prove (and have proven) to be a valuable indicator. He is very savvy about TMs. He sees them as an additional tool in the battle, one that has to be used with the utmost of proficiency and experience. He is very adept at deciphering who they are a valuable indicator for. But he would never know were he to not run them and follow them from setting a baseline post initial DX. His approach is to attempt to do everything possible to battle this disease, and finding out if TMs are indicative of activity and a valuable tool for an individual patient falls under "everything possible." For many (like me) they have proven to correlate directly to activity.

Maybe this is a very simplistic cliche', but for me it is basically "there is no way to know if you don't try...". Personally, I believe the stakes are too high to rely on statistics and generalized studies as the basis for my surveillance.

[AlaskaAngel]

After seeing how wrong the scientific community was over time about the risks and benefits involved with the use of the combination of estrogen and progestins, I look closer at their guidelines and recommendations to see how well they match up with "common sense" as well as whatever studies have been done.

I respect the basis for someone who is pretty thoroughly educated about breast cancer to make strong efforts to be sure people here know what the recommendations are, and provide some explanation for the basis behind them. I think that is admirable.

On a personal level, for me the rationale based on common sense holds water even for those who are diagnosed wtih high-risk early stage bc , or "primary" bc.

My rationale is this: If as an early stage breast cancer patient I am considered at high enough risk to be expected to accept and follow through with such toxic and expensive and difficult treatment as chemotherapy and radiation and synthetic antihormonal treatments, then I am at high enough risk for recurrence to be offered the right to periodic measurement with reasonably useful TMs such as CA 15-3 and CA 27.29. And of course I feel the same about anyone diagnosed with higher stage bc

One might argue that after having treatment I am at less risk so less likely to benefit from periodic marker testing. But given that we are currently still stuck with hardly any targeted testing at time of diagnosis, and because the current blanket approach with treatment only works for some (with resistance known to develop to treatment), I feel marker testing is truly justified -- especially since it is relatively inexpensive and nontoxic.

Regardless of whether markers improve survival (although I suspect they do now for HER2's to some degree, with more recent treatments), there are other reasons to want to know if one is progressing that are very relevant.

It would be interesting to see what the professional recommendations would be if they were made by a group of professionals who had undergone treatment for breast cancer.

AlaskaAngel

[Lani]

ASCO Issues Updated Recommendations For Breast Cancer Tumor Marker Testing [American Society of Clinical Oncology]
ALEXANDRIA, Va. — The American Society of Clinical Oncology (ASCO) has updated its clinical practice guideline on the use of tumor markers in breast cancer. The guideline authors observed that although researchers have made progress in developing tumor markers in areas such as diagnosis and treatment planning, mammography remains the gold standard in screening for breast cancer.
A tumor marker is a substance found in a person's blood, urine, or body tissue. The presence of a tumor marker, or higher- or lower-than-normal levels of a tumor marker, may indicate an abnormal process in the body, such as cancer, and can provide further information if cancer is diagnosed. Doctors may suggest tumor marker tests at various stages in the diagnosis or treatment of cancer. These tests can provide helpful information about both the cancer and the treatment.
"Increased use of tumor markers represents a shift in our understanding of the basic biology of breast cancer, which will affect how we treat patients," said guideline co-author Lyndsay Harris, MD, Vice Chair of ASCO's Tumor Markers Expert Panel and Associate Professor and Director of the Breast Cancer Disease Unit at Yale University. "The cancer research community needs to continue to conduct more clinical trials to examine exactly how tumor markers can help with the early detection of breast cancer."
To update its clinical practice guideline, first published in 1996 and subsequently updated in 2001, the ASCO expert committee reviewed the use of tumor markers in breast cancer and made recommendations based on their effectiveness for early detection of the disease, as well as their benefit in helping to plan treatment, monitoring response to treatment, and determining a patient's prognosis.
Much progress has been made in the area of tumor markers over the past 10 years. Since the 2001 guideline, researchers have identified six new categories of tumor markers. Although currently there are insufficient data to recommend the use of any of these new tumor markers in diagnosing breast cancer, both ER/PR and HER 2 testing are still recommended for diagnosis, as noted in previous versions of this guideline. However, two new tumor marker tests were recommended for their use in determining a breast cancer patient's treatment or whether or not breast cancer is likely to return after initial treatment.
The updated recommendations covered two new tumor marker tests for patients with newly diagnosed node-negative breast cancer, or cancer that has not spread to the lymph nodes.
The Oncotype DX tumor marker test is recommended for patients with node-negative breast cancer that is ER-positive and/or PR-positive, which is the case for 50 percent of breast cancer patients. The test measures multiple genes at once to estimate the risk of breast cancer recurrence. Patients with a low recurrence score may be able to receive only hormone therapy and avoid chemotherapy. Sparing patients from unnecessary treatment may not only improve their quality of life, but it also will reduce overall health care costs.
Other tumor markers that doctors can test are urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) markers. Testing these tumor markers can help estimate a patient's prognosis. Patients with tumors that do not have uPA and PAI-1 have a good prognosis and may not need chemotherapy. However, the test is not currently commercially available in the United States, but it is in Europe. More studies of this tumor marker are currently under way.
The guideline also encourages patients to enroll in clinical trials that focus on the use of additional tumor markers as a surveillance tool for breast cancer.
"Tumor markers can predict whether or not a patient will respond to treatment," Dr. Harris said. "The goal of these guidelines is to help doctors provide their patients with the best possible care. Patients will benefit from knowing whether or not a treatment will help them before beginning the treatment regimen."

[Lani]

OPEN ACCESS: REPORT: American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer [American Society of Clinical Oncology]
Purpose: To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer.
Methods: For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and metaanalyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations.
Recommendations and Conclusions: Thirteen categories of breast tumor markers were considered, six of which were new for the guideline. The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29, carcinoembryonic antigen, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, urokinase plasminogen activator, plasminogen activator inhibitor 1, and certain multiparameter gene expression assays. Not all applications for these markers were supported, however. The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells.

[hutchibk]

Well, there you go.

[dlaxague]

Brenda said:
Well, there you go.

Geeze, I've been trying to leave this alone (smile). But I'm not sure what you mean by that comment, because these guidelines repeat what I've been saying. Here's a link to the full text of the guidelines and for follow up after primary diagnosis, they are exactly the same as I've been mentioning all along (no benefit): http://jco.ascopubs.org/cgi/reprint/JCO.2007.14.2364v1

In addition, they say about the HER2 extracellular domain test (is that the same as the HER2 serum test, which I know NOTHING about and have no opinion on, please do not blame me for ASCO's opinion) again, the formatting's weird when I copy/paste:

Utility of circulating extracellular domain
of HER-2

Measuring circulating extracellular domain of HER2 is not currently
recommended for any clinical setting. There is no change from the

guideline published in 2000.

Debbie again - Brenda, Gina, FOB and others - are you going to SABCS this year? I'd like for us to meet, if you're willing. I suspect that we'll like each other better, in person. We all want the same things, after all - the best information there is available upon which to base a personal decision, and at least a basic understanding of that information for all women, right?

Debbie,
still wondering about the concept of zapping or surgically removing small organ mets as is done for those in the brain. Maybe a quick zap or procedure, and then some light chemo, herceptin, tykerb, or hormonal mop-up? Do you know if anyone's looked at that?

[hutchibk]

Hi Debbie,

"The following categories showed evidence of clinical utility and were recommended for use in practice: CA 15-3, CA 27.29... Not all applications for these markers were supported, however... The following categories demonstrated insufficient evidence to support routine use in clinical practice: DNA/ploidy by flow cytometry, p53, cathepsin D, cyclin E, proteomics, certain multiparameter assays, detection of bone marrow micrometastases, and circulating tumor cells."

This sounds to me to support evidence of clinical utility and that certain ones are recommended for use in practice. (My TMs are specifically CA 15.3.), Am I reading it wrong? Is there something between the lines that I should be interpreting differently, or can I take those words at face value? I guess I haven't made my personal opinion, research and preferences clear enough, which are: there are oncs who don't defer to generalized studies and guidelines, and who use specific TMs in the clinical setting, who are adept at following them and applying them to patients whom they apply to, following their theory of individualized treatment. I heartily hail these docs (and mine is one).

Yes I will be at SABCS. It will be good to meet everybody.