Question about strategy for more adequate testing with minimal expense

[AlaskaAngel]

I don't want to divert the interesting discussion under Lani's post about the real world testing, but I have a similar question about present methods of testing.

Wouldn't it make better practical sense to routinely administer at least a CA 15-3 or a CA 25.29 (even though not wholly reliable) to those with particularly dense breasts whose mammogram and ultrasound are inconclusive, rather than having them "come back in 6 months" for a repeat mammo/ultrasound?

Whenever anyone I know has an inconclusive result like that, especially if they have other risk factors, I advise them to push their PCP to provide permission for that to be done.

-From this patient, whose insane original "breast cancer specialist" and fully qualified surgeon only did a biopsy after three successive BIRADs 4's, each several months apart, even though I had a huge family history of bc.

[suzan w]

I agree, AA. A dear friend of ours, age 37...has been trying to get to the bottom of strange pains, heaviness, etc. for over a year now. Despite strong family history of BC, she finally got her first mammo a month ago (she is "not 40" grr) and it came back inconslusive. I have strongly advised her to get the tests you mentioned. Whe wait another year, fight with insurance co for another mammo...

[AlaskaAngel]

Thanks, Suzan! I'd like to think that someone who has some authority to make the test available routinely in that circumstance is at least as smart as we are.... but so far I dunno...

One reason in particular that I think they are not thinking as clearly about that question is that possibly they are basing their opinion about the unreliability of the testing upon patients whose results are most often quite likely to be less reliable due to most of them having usually had recent chemotherapy prior to the use of the those tests. I know my results for the CA 15-3 or CA 27.29 were higher due to chemotherapy and it wasn't until a while after the chemo cleared before the tests settled down to steady low results.

Thus I think those tests might be a lot more reliable than they realize, particularly for undiagnosed patients and treatment-naive patients and patients who are far out from treatment -- like me.

A.A.

P.S. It seems to me they have been thinking about use of it only after the horse has gotten out of the barn and they haven't given any real thought to using it preventatively.

P.P.S. Not only that, but it could potentially reduce the amount of rads we get over time, if it proves to be as reliable as mammos. (When one is 10 years out, it starts to add up.....)

[Lani]

Int J Cancer. 2012 Aug 7. doi: 10.1002/ijc.27766. [Epub ahead of print]
Identification and validation of a new autoantibodies for the diagnosis of DCIS and node negative early-stage breast cancers.
Lacombe J, Mangé A, Jarlier M, Bascoul-Mollevi C, Rouanet P, Lamy PJ, Maudelonde T, Solassol J.
Source
CHU Montpellier, Arnaud de Villeneuve, Department of Cellular Biology, Montpellier, France; University of Montpellier I, Montpellier, France; CRLC Val d'Aurelle, Department of Clinical Oncoproteomics, Montpellier, France.
Abstract
Evidence of circulating autoantibodies in cancer patient sera has created opportunities for exploiting them as biomarkers. We report the identification and the clinical validation of an autoantibody panel in newly diagnosed patients with early-stage breast cancer. Proteomic approach and serological screening of a discovery set of sera (n=80) were performed to identify tumor-associated antigens (TAAs). Autoantibody levels were then measured in an independent validation set (n=182) against a panel of five TAAs by enzyme-linked immunosorbent assay. Sixty-seven antigens that elicited a specific humoral response in breast cancer were identified and five antigens (GAL3, PAK2, PHB2, RACK1, and RUVBL1) were selected for validation. GAL3 and RACK1 showed significantly increased reactivity in early-stage breast cancer. When combined, the five markers significantly discriminated early-stage cancer from healthy individuals (AUC=0.81; 95% CI [0.74-0.86]). Interestingly, this value was high in both node-negative early-stage primary breast cancer (AUC=0.81; 95% CI [0.72-0.88]) and ductal carcinoma in situ (AUC=0.85; 95% CI [0.76-0.95]) populations. This autoantibody panel could be useful as a diagnostic tool in a screening strategy of early-stage invasive breast cancer and pre-invasive breast cancer. It could be particularly appropriate in complement to mammography for women with high breast density. © 2012 Wiley Periodicals, Inc.
Copyright © 2012 UICC.
PMID: 22886747 [

[AlaskaAngel]

Thanks, Lani!

I think it is also interesting to see just how often these kinds of questions seem to be investigated first primarily by overseas researchers.

A.A.

[Debbie L.]

I've been meaning to weigh in on this interesting discussion for awhile.

AA asks: "Wouldn't it make better practical sense to routinely administer at least a CA 15-3 or a CA 25.29 (even though not wholly reliable)") . . .

My answer to you, AA, would be that those two markers are even less than "not wholly reliable" when used as a screening tool.

Here's what a 2007 medline reference says:
"Currently, insufficient data exists to recommend the use of CA 15-3 measurement for screening, diagnosing, or staging breast cancer.[6] CA 15-3 levels are elevated infrequently in early-stage breast cancer or completely absent from other breast cancers, making it difficult to detect early-stage cancers or those tumors that do not express this antigen. However, several studies report prognostic value of the CA 15-3 marker in early-stage breast cancer.[6, 7] Presence of this tumor marker may predict a worse outcome, but the implication on management of early-stage breast cancer remains unclear. This marker has no clinical value in breast cancers that do not produce the CA 15-3 marker.
CA 15-3 levels may also be increased in several benign and malignant conditions. This results in low sensitivity, specificity, and positive predictive values, making it difficult to reliably screen, diagnose, or stage breast cancers. The CA 27.29 assay is slightly more sensitive for breast cancer, but its indications and limitations are identical to the CA 15-3 assay.[6]"

In discussion of the same issue, breastcancer.org says only 30% of those with primary breast cancer will have elevated CA 15-3 levels.

Plus, false positives are common and can be caused by other conditions than cancer, or by cancers of non-breast origin.

I think there is a fair amount of research interest right now in a better marker (or markers, like in the article Lani posted) for screening for breast cancer.

I don't want to be a total wet blanket here, but several things about this concern me. First of all, we still don't really know how early is early enough, for the most aggressive cancers. There may be a segment of cancers that metastasize nearly immediately, making those breast cancers a systemic disease long before they are detectable. The inability of all this research to show a strong benefit to mammography is supporting evidence for this idea.

My second concern is that if we detect a breast cancer TOO soon with a blood test, we don't know what to do about it. We don't know how big a threat it is or has the potential to be. We don't know if it has to be surgically removed or if some kind of systemic treatment could nip it in the bud. What if (and this would happen frequently) a blood test indicated breast cancer, but no lump could be found? Would we begin lopping off both breasts of all women who receive a positive result?

I wish we had better answers -- I wish we had a reliable method of very early detection and the knowledge of what to do with that information, to save lives. But we don't have that information. At this point, it is possible that all we'd do with earlier detection is cause a whole lot of anxiety, spend a whole lot of money, and cause suffering (treatment) -- all with no lives saved in the end. I think we need to think carefully before we get too far down this road.

I've come to believe that the answer doesn't lie in this direction. I agree with NBCC that the answer lies in prevention of primary disease and prevention of metastasis.

Debbie Laxague

[AlaskaAngel]

DebbieL,

I am happy to see an alternative such as Lani's post too!

You and I sometimes differ, but all in the pursuit of better care, as I know that to be your goal as well as my own.

However, when it comes to discouraging the use of the CA 15-3 or CA 27.29 in the meantime, while continuing to tell women to "come back in 6 months" for a repeat mammo and ultrasound in these circumstances, I am less inclined to lean toward avoiding the use of these tests despite their track record for accuracy, particularly since as you note, the need is not limited to those who are in fact early stage at time of analysis. When you add those particular patients to the patients whose cancers may be early stage but are highly aggressive cancers and yet remain undetectable by mammogram and ultrasound at that point, an actual clinical trial for the use of these tests for patients to have the choice of "wait and see" or "get the test" might show more value than basing the judgement upon only the reliability of them.

A.A.