Topoisomerase-IIa as a Predictor of Anthracycline Response

['lizbeth]

I'm just curious why TOP2A testing was FDA approved in January 2008, but most of newly diagnosed don't seem to be aware of the test.

Why have an increased risk of cardiotoxicity and leukemia unless you know Adriamycin is more effective for your type of cancer?

Am I missing some additional information on the reliability of this test?


http://www.cbcrp.org/RESEARCH/PageGr...?grant_id=4848

[AlaskaAngel]

'lisbeth,

Like you, I wonder if there is some weakness to the test that isn't obvious?

But at the same time.... consider that it took a long time before testing for HER2 was more routinely done by oncologists (and it appears from some posts that even THAT still is not done as routinely as it should be!)

At time of diagnosis the learning curve is pretty steep and if there isn't much publicity about a test it gets lost in the shuffle. I hope to see my surgeon soon and will ask him about this, and whether the cancer center routinely uses the test or not, and if not, why not...

Maybe some others could do the same, and see what the consensus is about this?

AlaskaAngel

[dlaxague]

That anthracyclines have no place in adjuvant therapy today, except in countries where Herceptin is not available. He says that anthracyclines offer additional benefit only to topoIIa+ cancer. BUT all topoIIa+ cancer is also HER2+ and thus these cancers will be treated with Herceptin (I think he prefers TCH) and so they need no anthracycline anyway (because when Herceptin is used, there is no additional benefit to using an anthracylcline, whether topoIIa+ or not). Since anthracyclines increase the risk of leukemia and heart damage, and do not offer any additional benefit to anyone, over standard chemo, there is no place for them in adjuvant treatment today, thus there is no reason to test for topoIIa. Says Slamon.

Others, the cautious ones, want to see more evidence. They are not convinced that topoIIa+ is limited to those who are also HER2+. They are not convinced that anthracyclines do not offer additional benefit to any aggressive or higher-stage cancer. They wait for more studies to be published.

I don't know who is right. My opinion is that what Dennis Slamon is saying makes good sense.

So my guess at the answers to your question:

1. The onc shares Slamon's thoughts and does not use anthracyclines anyway, so there's no reason to know topoIIa status.

2. The onc is cautiously awaiting more evidence of either:
a). a link between increased response to anthracyclines and topoIIa status.

and/or

b). evidence that Herceptin + any standard chemo is equivalent to Herceptin + anthracycline.

Debbie Laxague

[AlaskaAngel]

Deb,

By saying that, is Slamon (and are you) also saying that the exact same HER2 positive persons who might be resistant to Herceptin never benefit from Adriamycin more than they do T & C, even if they are TOPO IIA?

I'm no fan of Adriamycin -- but just trying to figure out if he is saying that those HER2s who are TOPO IIA and fail on Herceptin would not ever benefit more from Adriamycin (because the T and C alone work better (?) or as well (?) for those who fail on Herceptin than Adriamycin, even though they are TOPO IIA?)

Thanks,

AlaskaAngel

[dlaxague]

That's ANOTHER one of my questions - exactly what you're asking, AA. Although when I try to ask it, most people do not understand what I'm asking.

In the adjuvant Herceptin trials that have reported so far, there doesn't seem to be any additional benefit at all to and anthracycline with Herceptin. But if what we're asking is true, shouldn't we see a small benefit, from that (possibly, if topoIIa is random) 1/6 of those getting Herceptin (who did not benefit from Herceptin but were topoIIa+ and so reaped additional benefit from the anthracycline)? Either that subgroup is too small to affect the larger group's stats, or there's something wrong with the hypothesis - either Slamon's or yours and mine.

Debbie

[Jean]

Lizbeth, I understand your frustration on the delay in new testing being available. It seems it takes time for new testing to take a hold. This reminds me of the Oncotype DX testing for those who were on the fence with having chemo and it took a long time before centers began using the test...just a short while back many onc. said it was not standard care of treatment.

When I saw Dr. Slamon he insisted that I have the topo2a test prior to making any decison on chemo.
Because, if topo2a positive than A/C would be okay to go with, if negative (and I was neg.) A/C would not have benefit for me. Dr. Slamon was the only one at the time 2006 to offer the test. Most dr. did not even know about it and those who did (even now) do not use it.

Last year at the BCS Becky and I went to a lecture that Dr. Slamon was giving and I will share that the topo2a
was a much heated topic. Dr. Slamon has been saying for the last few years that the topo2a should be tested before making a treatment decison. Yes, he does favor
TCH .....since the trials proved to be desirable.

Why does it take so long? I can only answer when it comes to Dr. Slamon, long before the FDA approved
herceptin to ALL her2 women (remember early stagers)
were not approved and had to fight for it and get it off label and pray the insurance would cover the cost.
Dr. Slamon was saying...."All Her2 women should be given herceptin" how many did not agree with him.
Shocking isn't it? I am thinking it is the same with the topo2 ...and in a year or maybe two we will be reading
how topo2 is routine. Very frustrating...

Just recently I posted a medical article stating how STILL some women are NOT tested for HER2, can you believe that?

I want to know why testing for HER2 is not routine
on DCIS?

I hope this information helps.
Jean