TOPO2 test?

[DianneS]

Can someone tell me what this test is, providing I have spelled it correctly

Can any bc patient receive it?

Thank you,
Diannes

DX: Aug. 08, IDC right breast 2.1 cm tumor, weakly ER positive, PR negative, her2 positive+++, NO positive lymph nodes, left breast ok.
Bilateral mastectomies: Sept. 08
First dose of Herceptin yesterday-did fine, Taxotere caused reaction so have to wait to see what the docs are cooking up next week for me....hopefully I can still do the TCH regimen.....

[Jean]

Dianne,
This test (topo2a) was recently approved in the US by our FDA...this test (it is still not standard practice yet)
determines if you are negative or positive for the
Topo2a which is a gene.


If you are topo2A positive than A/C chemo could be a choice...if you are topo2a negative you would have
resistance to A/C and it would serve little or no benefit.
This test has relevance to anthracycline treatments and can have dramatic effect on response to therapy.
There is new data suggesting a complex link between Her2 and TOPO2a genes in breast cancer.

I had the test and was negative - hence I had TCH
this treatment is becoming the standard especially for
early stage bc.

[DianneS]

My onc gave me the results during chemo (TCH) of my test. I think she said it was 65% something and 35% something else - now I can't remember what....but she indicated it was good. Now I have to figure out what the heck she was babbling about. Wouldn't she have done this test BEFORE chemo?

I did four and a half sessions of the TCH (could do five and a half, but why?) and am tortured by whether it's enough. She keeps calling my breast cancer 'early' even though the tumor was 2 cm. I can't get 6 sessions because I had a half session that counts as a full session or some such mumbleypeg.

So, what should I specifically ask her about the topo2 results?

I thought anything under 1 cm was 'early'.

[Debbie L.]

There is nothing decided about the significance of topo 2a expression/amplification. You can find respected oncologists on either side of this argument, which tells me that the jury is still out, and in addition - that the difference/significance, if any, is probably not huge. There are all kinds of arguments - whether the assays are looking at the right thing (is it overexpression, amplification, or something else altogether that is a marker for additional anthracylcline benefit), whether topoIIa+'s can be HER2 negative, etc.

Dennis Slamon, who is respected especially in the HER2 community for his amazing work in studying HER2+ cancer and in developing Herceptin, believes that there is no place for anthracyclines in current adjuvant treatment for breast cancer. This is especially interesting because he's been one of the most interested people in the investigation of topoIIa r/t anthracyline response. He supports his anti-anthracycline stance by citing evidence to support the idea that anthracycline chemos offer an additional advantage over other chemos only to those who are topoIIa positive. BTW, it is NOT that anthracyclines do not "work" for topo2a negative cancer - it is that (according to this theory) topo2a negative cancers do not receive an ADDITIONAL benefit from anthracyclines, over other chemos. TopoIIa negative cancers do respond to anthracyclines, just as they do to other chemos. But if there is no additional benefit to an anthracycline and there is an addition to the side effect profile (mainly heart damage but also leukemia) when anthracylines are used - who would choose that?

So, again - continuing with Slamon et al's theory: He thinks that only HER2+ cancers (about 1/4 of them?) are topoIIa+. He says that if Herceptin is available, it trumps the anthracycline and so there is no place for an anthracyline when Herceptin is available, even for topoIIa cancers.

So, if you subscribe to Slamon's theory about topoIIa - you can only be topoIIa+ if you are also HER2+ and if you are HER2+, you'll get Herceptin and so there is no reason to know the topoIIa status because with Herceptin in the picture, an anthracycline offers no additional benefit to topoIIA+ cancers.

OTOH, other respected experts say that there is not enough evidence to support Slamon et al's claims. They say that there are reliable studies that show that it's possible to be topoIIa + and HER2-, in which case an anthracycline could (perhaps) offer additional benefit. They say that for high risk cancer, all evidence still points to an additional benefit from an anthracycline-based chemo, and they are not ready to deny this possible increased benefit to their high-risk patients, whether HER2+ or HER2- and whether topo2a + or - . They don't say that Slamon is wrong necessarily, but they do say that there's not enough evidence to say that he is right, and they do not want to deny their patients possible benefit until they know for sure.

Slamon's argument sounds plausible to me, when I hear him argue it. But then - so does the opposition's argument. I guess I'm gullible. Frustratingly, Slamon has not published his results even though he has been talking about this for years.

I don't know the answer. I've given myself brain fatigue just trying to write this semi-intelligibly. But when the argument among the big guns and the brilliant minds goes on this long, it makes me think that the answer is not going to show a very big difference either way, especially in the presence of Herceptin.

DL

[Laurel]

That was really interesting and well worth the brain fatigue, so thank you. I requested the TopoII test back in April prior to beginning chemo. It was so very difficult to decide between the ACTH and the TCH. I am located in the East and the TCH hasn't fully caught on here. My Onc. said the test wasn't commercially available and that I'd have to pay out of pocket to a private lab. I wish Dr. Slamon would publish his study so more Oncs can reference it. It will forever lurk as an unanswered question for those who chose the ACTH.

[Debbie L.]

I have not looked at more than the abstract but this is reportedly a 300+ (!) page discussion of HER2 testing from AHRQ, hot off the press. If you fast-forward to the last paragraphs of the abstract, it seems that it took them 300 pages to say that we don't know most of the answers to all of the questions (anthracycline/HER2/topoIIa, tamoxifen vs. AI with HER2+, serum HER2, etc).

http://www.ahrq.gov/clinic/tp/her2tp.htm#Report

Structured Abstract

Objectives: Systematic review of trastuzumab outcomes among breast cancer patients who have negative, equivocal, or discordant HER2 assay results; use of HER2 assay results to predict outcomes of chemotherapy or hormonal therapy regimen for breast cancer; use of serum HER2 to monitor treatment response or disease progression in breast cancer patients; and use of HER2 testing to manage patients with lung, ovarian, prostate, or head and neck tumors. Also, narrative review of concordance of HER2 assays.

Data Sources: We abstracted data from: three articles plus one conference abstract on negative, equivocal, or discordant HER2 results; 26 studies on selection of chemotherapy or hormonal therapy; 15 studies on serum HER2; and 26 studies on ovarian, lung, prostate, or head and neck tumors. Foreign-language studies were included.

Review Methods: We sought randomized trials or single-arm series (prospective or retrospective) of identically treated patients that presented relevant outcome data associated with HER2 status.

Results: HER2 assay results are influenced by multiple biologic, technical, and performance factors. Many aspects of HER2 assays were standardized only recently, so inconsistencies confound the literature comparing different methods. The evidence is weak on outcomes of trastuzumab added to chemotherapy for HER2-equivocal, -discordant, or -negative patients.



Evidence comparing chemotherapy outcomes in HER2-positive and HER2-negative patient subgroups may generate hypotheses, but is too weak to test hypotheses. Only a rigorous test can resolve whether HER2-positive patients (but not HER2-negative patients) benefit from an anthracycline regimen. Evidence is available only from uncontrolled series on whether HER2 status predicts complete pathologic response to neoadjuvant chemotherapy.


Evidence also is weak regarding differences by HER2 status for outcomes of chemotherapy for advanced or metastatic disease; with most studies lacking statistical power. Data from studies of tamoxifen and aromatase inhibitors suggest that future studies should examine whether HER2 status predicts response to specific hormonal therapies among estrogen-receptor-positive patients.


The evidence is weak on whether serum HER2 predicts outcome after treatment with any regimens in any setting, as is the evidence on use of serum or tissue HER2 testing for malignancies of lung, ovary, head and neck, or prostate.

Conclusions: Overall, few studies directly investigated the key questions of this systematic review. Going forward, cancer therapy trial protocols should incorporate elements to facilitate robust analyses of the use of HER2 status and other biomarkers for managing treatment.