[Debbie L.]

Thanks for that, Joe. Great presentation. So convincing. There are other experts in the field who still seem unconvinced though, and when I listen to them, THEY sound convincing also. I guess I'm just gullible.

But what Slamon is saying (and has been saying for years now) is that topoIIa is of no importance for those in a country where HER2+ cancers will be receiving adjuvant Herceptin. He's saying that all topoIIa+ cancers are HER2+. TopoIIa+/HER2+ cancers get equal additional benefit from EITHER an anthracycline OR Herceptin (there is no added benefit if they are given together and there is significant added harm in the form of cardiac effects).

So for adjuvant treatment, if you're HER2+, you'll get Herceptin and so you have no need to know if you're topoIIa positive. He didn't discuss mets and I don't know the answer there. Would it be worth knowing the topoIIa status of mets because if Herceptin failed, then an anthracycline might be the best bet? That seems like a reasonable question, although there are so many other options now that maybe it would be way down the line of choices.

He is saying that he thinks no more studies are needed. He shows the group that benefited greatly from anthracyclines and it's that tiny HER2+/topoIIa+ group (before Herceptin). Their benefit was large enough that it skewed the whole group of all breast cancer to make it look as if anthracyclines offered additional benefit to all. But that was before we knew that we had subgroups to look at. Now that we know some subgroups, and they have been looked at - we know that anthracyclines do not offer additional benefit to anyone but the ones who are now getting the same benefit for Herceptin and thus do not need an anthracycline.

Is this making any sense?

The arguments that say Slamon doesn't have enough proof talk about several things. I've heard it argued that in order to be a fast-growing cancer, topoIIa has to be "active" and that activity of topoIIa may happen in the absence of amplification/overexpression so there still could be an advantage to using an anthracycline in HER2- aggressive cancers, particularly triple negative ones. A theory. I don't really understand what they mean by "active" but that's the argument. But no one seems to be arguing that there's a place for anthracyclines for HER2 positive cancers (when Herceptin is available). Thus, for HER2+ cancers who will receive adjuvant Herceptin there is also no place for topoIIa assays.

So - what about lapatinib? I hope that they're looking at topoIIa now, in the newer studies. The fact that most of the evidence so far is retrospective is another argument used against Slamon's certainty.

It seems like most of the opposition is not saying he is wrong exactly - they're just saying they want to see more/better evidence that he is right, before changing their practice.

Debbie Laxague