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At the American Society of Clinical Oncology (ASCO) annual meeting, a presentation titled "Are We Splitting the HERs? The Highs and the Lows" examined three posters related to low HER2 to try and determine if pathologists are adequately quantifying the HER2 immunohistochemistry (IHC) assay.

In this exclusive 51成人动漫 video, David Rimm, MD, PhD, an Anthony N. Brady Professor of Pathology at the Yale University School of Medicine in New Haven, Connecticut, details his presentation.

Following is a transcript of his remarks:

I'll be presenting a poster discussion on low HER2. The title is "Are We Splitting HERs?" -- a pun on hairs. But splitting is because the new drugs, the ADC [antibody-drug conjugate] trastuzumab deruxtecan [Enhertu], is indicated for patients that have HER2 1+ or 2+ IHC, but not HER2 0. And the question is, can we split those?

And we've published extensively on the fact that pathologists can't really tell those apart. And so now I'm asked to review three discussions on posters related to low HER2.

The first of which is related to I-SPY, which has a great collection of patients with low HER2 because many of the triple-negative patients that were in the I-SPY trial. But unfortunately that was all done at a time where pathologists weren't asked to tell the difference between a 0 and a 1. So they don't see any difference, which is not a surprise to me because the pathologist can't make that distinction. So that distinction doesn't show up when you do a retrospective study.

Then the second study I'm reviewing is a study related to mRNA expression, which shows the dynamic range of low HER2 improves by mRNA, that there really is a completely separate peak of HER2 expression in the lower range, not in the amplified range, which is the traditional range for trastuzumab treatment. And that was interesting. That study also shows that the RNA levels are not different between the IHC 1's and the IHC 0's and the IHC 2's. There's a little bit of an increase in trend, but it also shows the pathologist's inability, retrospectively, to be able to "split hairs."

And then the last study is a study looking at another way of quantification of the HER2 IHC assay. And they actually do find that they can tell differences. And it's just an example of what I think is the future, which is using mechanisms including both RNA and protein expression quantification to determine when a HER2 patient has no HER2, and when they have above the limit of detection or limit of quantification.

In fact, I will spend a little time talking about our work, which described an assay that is more sensitive for HER2 we call HS, or high-sensitivity HER2, which can tell the difference between 0's and 1's. Treating HER2 like an analyte, like a chemistry, sodium or potassium or a glucose, where instead of in mgs/dL, we describe HER2 in atom moles/mL². And atom moles/mL² is something that's similar to a concentration but is spatially informed because it's on a slide.

We're going to need to use other methods. We're going to have to measure, not read. That is, we'll have to use more technical methods to determine the actual HER2 levels, either by protein or RNA, as opposed to have pathologists' judgements, which are just insufficient with the current assay to be able to distinguish a 0 from a 1.

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