[Debbie L.]

Good morning. Happy anniversary to all.

I remember asking the same question (what does level of HER2 mean) and not getting any answers. I thought I remembered a good explanation of this on this website but I can't find it this morning. Maybe someone else knows the way?

First of all, HER2 +++ (3+) is the report from one way of testing for HER2. Cancers that test 1 or 2+ (+, ++) by this method (IHC) are not considered to be HER2 positive, although the 2+ ones are usually double-checked by another method (see below). So almost, if not all of us on this list have or had HER2+++ (3+) cancer. Reporting it as HER2 +++ simply means "HER2 positive". That doesn't really say anything about how much HER2 there was, compared to other HER2 positive cancers.

But as with everything else, it's not quite that simple. The newer (but not necessarily better) test for HER2 is called FISH, and it reports out a number (a ratio but it's written as just a number). For that test, above 2 is usually considered HER2 positive. As I said above, if the IHC test is done first and comes back 2+ or 3+, typically it's double-checked with a FISH assay. The FISH report does quantify the amplification of HER2. So you'll see HER2+ that has a FISH of 2.5 and those that have FISHes well above 10 -- a wide range and all are "HER2 positive". Most of the research that has tried to link the level of FISH to either outcome (prognosis) or response to Herceptin has not been able to see any correlation.

To further muddy the waters, it's interesting that they are actually doing studies now of HER2 targeted treatments (Herceptin and/or vaccine) for those who are technically considered HER2 negative but are now being called "HER2 low expressing" because the cancer has some HER2 (1 or 2+) but not enough to be called positive by current standards (less than 2 on the FISH assay).

Here's a pretty good explanation of the tests, if you want to know more, but it doesn't answer your question either (smile). http://www.nccn.com/about-nccn-com/6...-category.html

There have been a few small studies that seemed to find some correlation between HER2 level and outcome (or response) but most have not. I did see something very recently about response to TDM-1 being better in higher levels of positivity. Okay, here's one write-up of that (it was at AACR), and it's not FISH they used. They tested for HER2 in yet another way (mRNA). They only report differences in response for the T-DM1 arm, not for the xeloda/tykerb arm. Or at least, if that was different, it's not mentioned in this article. One subgroup analysis is not enough to give us an answer but I'm sure they will keep looking. http://www.oncologynurseadvisor.com/...ticle/288201/#

So the answer to your question is sort of "no". First of all, 3+ is not necessarily "high", it's just positive. And if it were high, we don't know what that means but probably it doesn't mean anything, or someone would have figured it out by now.

Debbie Laxague