Link to 2007 ASCO guidelines for tumor markers

11-27-2007, 05:14 PM

http://jco.ascopubs.org/cgi/content/full/25/33/5287

Gerri · 11-27-2007, 06:37 PM

Grace,

Perfect timing! I see my onc on Dec 7 and was planning on discussing tumor markers (she doesn't do them) and Tamoxifen vs. AIs. I quickly glanced over this and will go back later and read it more carefully to make sure I understand all the details.

Thanks for posting this link!

hutchibk · 11-27-2007, 07:30 PM

yup...

2007 recommendation for CA 15-3 and CA 27.29 to contribute to decisions regarding therapy for metastatic breast cancer. For monitoring patients with metastatic disease during active therapy, CA 27.29 or CA 15-3 can be used in conjunction with diagnostic imaging, history, and physical examination. Present data are insufficient to recommend use of CA 15-3 or CA 27.29 alone for monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CA 15-3 or CA 27.29 may be used to indicate treatment failure. Caution should be used when interpreting a rising CA 27.29 or CA 15-3 level during the first 4 to 6 weeks of a new therapy, given that spurious early rises may occur.

It will also be interesting to see what new studies and recommendations might come out of SABCS re: CTCs and CA 15-3 / CA 27.29 to detect recurrence after primary breast cancer therapy.

dlaxague · 11-27-2007, 09:07 PM

Gerri, if you're looking for support for doing tumor marker or scans as part of follow-up after primary disease, you're not going to find it in this guideline. You may find it in this forum - there has been lots of discussion and some excellent points made - for example that there is not good current information to support either view. But this guideline does not recommend tumor markers for follow-up of primary disease. It says:

"2007 recommendation for CA 15-3 and CA 27.29 to detect recurrence after primary breast cancer therapy. Present data do not support the use of CA 15-3 and CA 27.29 for monitoring patients for recurrence after primary breast cancer therapy. There is no change from the guideline published in 2000. Literature update and discussion. Several well-designed studies have shown that an increase in CA 15-3 or CA 27.29 after primary and/or adjuvant therapy can predict recurrence an average of 5 to 6 months before other symptoms or tests. While additional studies have been published since the last ASCO guideline that address the value of these serum markers at detecting recurrence,there are no prospective randomized clinical trials to demonstrate whether detection and treatment of occult or asymptomatic metastases using tumor markers impact on the most significant outcomes (disease-free survival, overall survival, quality of life, toxicity, or cost-effectiveness). Although the assay was approved by the US Food and Drug Administration, the US Food and Drug Administration does not require tests to show clinical benefit if that is not part of the manufacturer's indication. Given the limited evidence, and until clinical benefit is established, present data are insufficient to recommend routine use of CA 15.3 or CA 27.29 for this application. This recommendation is in line with that of the ASCO guideline for follow-up and management of patients with breast cancer."

Me again - There are many oncologists who do use tumor markers and scans as part of follow up after primary disease. At this point, there's no evidence to support using them and so I'd say it remains an individual decision. The users say that it should be better to find a cancer recurrence before symptoms herald its presence, even though the studies, so far, do not support that claim. The non-users point to the studies that show no difference to length of survival nor to quality of life when a recurrence is found with markers before symptoms are present. And they add that doing the tests can cause anxiety and also can lead to more unecessary (and negative) testing. And that a negative test result offers no guarantees.

I am a non-user. While I of course do not like the idea that I could have a recurrence, and I wish that I had more control over my outcome - I find some peace in believing that ultra-vigilance will offer me no benefit. I get my small fix of control-illusion by knowing what symptoms might be worrisome, and knowing to report them if they last longer than two weeks, or sooner if they are severe. This style works for me. I do not have to endure the anxiety of anticipating the test, nor of waiting for the results. I do not have to deal with the heightened level of alert that accompanies "borderline" results. A negative test offers me no reassurance. I know that I could have a negative test today and mets next week. I have given up most illusions of control, which is both scary and at the same time, wonderfully liberating.

Think about what style of medical management works for you. Discuss this with your current oncologist and if you're not satisfied with the answers, get a second opinion. If you want to be ultra-vigilant, you can probably find a provider to assist you in that style of follow-up.

I hesitate to bring this up because it's such a touchy issue (in my experience, smile). But another factor to consider, if you're willing, is stewardship of available resources to pay for the incredibly expensive technology that is now available to us. This does not apply so much to tumor markers, which are relatively cheap, but it does apply to scans done simply to reassure an NED woman after primary disease (I am not talking about people with mets). It's fine to talk of the terrible state of health care in this country and say that we must demand the tests that we "want", expense be damned. But the fact is that we (the big "we" - our society) are not going to be able to afford to do everything for everyone. It's not something that anyone is glad about, but it's a fact that needs to be faced.

I don't have answers. But I do wish that more politicians were brave enough to raise the questions. The solutions are hard, and if they are to provide equitable care to all, those solutions probably must involve rationing of care.

Do you feel that you should try to be a good steward of health care dollars, or do you feel that your primary cancer diagnosis entitles you to whatever you want or feel that you need? I don't ask these questions because I know the answers to them, nor to challenge. I ask them so that we all stop to think about the big picture.

Debbie Laxague

Gerri · 11-27-2007, 09:42 PM

Hi Debbie,

After posting my quick response I realized that it seemed as if I were looking for an argument to use in support of running tumor markers and scans as follow up. Actually, what I found was more support for my onc's method of monitoring me (the national guidelines) and it reinforced my level of comfort. I have full confidence in my onc and always felt that constant testing was not for me. I am treated at a major cancer center in California (City of Hope) and have nothing but praise for the wonderful care I have received. The timing of this was perfect because I was going to ask my onc if there was anything new on the use of tumor markers - this answered my question before I could ask.

The bigger question for me all along has been the use of Tamoxifen vs. an AI. Each time I go for a check up we discuss my still (I'm 54) premenopausal status and the use of Tamoxifen. She has consistently told me that the current data does not overwhelming promote suppressing my ovaries and switching to an AI - again, these updated guidelines support her position. I am having my levels checked again before seeing her but will be perfectly comfortable with letting nature take its course.

I can see both sides when it comes to running markers and tests for early bc, but feel that the course my onc is taking is the right one for me. I have read with great interest the posts on this and know how strongly those who are tested feel about this form of follow-up. Passions run high on both sides of the fence.

Thank you for your input. I appreciate your views on this and always enjoy reading your posts.

Best regards,

11-28-2007, 09:39 AM

Gerri,

I am not ER positive so generally don't follow the research on estrogen-suppressing drugs. But recently, and I don't know where (perhaps here), there was something on AI causing bone density problems and a suggestion that women should not be taken off Tamoxifen so quickly . Apparently, Tamoxifen does not cause the same types of bone problems.

But then I also remember reading that AI is more effective with HER2 positive cancers. Again, I don't do research on this subject so it's just what I read as it comes across my computer, but you might check on the recent findings concerning AI and loss of bone density. Try a Google search.

Your decision to trust your oncologist concerning tumor markers is the decision I should have made, and didn't, and it's too late now. My recent results indicate that they are moving up (still within normal range, but just) and I am back to worrying. I agree fully with Debbie on her view of equity in medical care, although it's difficult to take the high road when one has been diagnosed with cancer. I'm glad some of us can do it and wish I had joined them, if only for selfish reasons.

Gerri · 11-28-2007, 10:02 AM

I copied the following from the article:

Literature update and discussion. Complex interactions exist between the HER2 and ER pathways. HER2 expression in human breast cancer cells is downregulated by estrogens.136 Conversely, overexpression of HER2 promotes estrogen-independent growth and is associated with resistance to tamoxifen in vitro and in animal models, possibly by promoting ligand-independent growth. These observations are consistent with the inverse association of estrogen and progesterone receptors with HER2 overexpression and also provide a rationale for the lower response of HER2-overexpressing tumors to endocrine therapy shown in several clinical studies.107,137-141 However, most of these studies were retrospective and nonrandomized. To date, randomized trials have not led to consensus on this association.142-145 The interaction of HER2 with endocrine therapy may vary depending on the type of hormonal agent in question. Ellis et al146 have shown that HER2- and/or EGFR-positive tumors were more likely to respond to neoadjuvant letrozole than tamoxifen in a randomized trial of 324 primary breast cancer patients. In contrast, an analysis (presented in abstract form only) of the Anastrozole versus Tamoxifen versus a Combination of the two (ATAC) trial, failed to show that HER2-overexpressing tumors benefit more from the aromatase inhibitor.147,148 In summary, there are insufficient data to support the use of HER2 in tissue (or serum, as discussed below) as a predictor of response to endocrine therapy, although the evidence does suggest that in patients with ER-positive tumors, the relative benefit from antiestrogens for those with HER2-positive cancers is likely to be lower than for those with HER2-negative cancers. It is not at all clear that the benefit of aromatase inhibitors in this group is any greater than in the HER2-negative, ER-positive group. 


To me this is confirmation that continuing with Tamoxifen until I naturally enter menopause is reasonable.

11-28-2007, 12:26 PM

Gerri--I knew I had read it somewhat very recently; and, of course, I read it in the guidelines that I actually posted. Wow, and I used to brag about my memory. No more of that!