HER2 Part 6: Agendia's TargetPrint Test

Bottom line: TargetPrint is a quantitative mRNA test that can be used as a second opinion to IHC or FISH testing or as a first line test to measure HER2, ER and PR.

There are three situations where it would be reasonable to consider some of the next generation, "non-standard-of-care" tests, like TargetPrint, that assess a breast tumor's HER2 status:

1) The first situation is when a basic IHC (immunohistochemistry) test like Dako's HercepTest gives an "equivocal" result (a score of 2+). Today FISH is most commonly used in this case. But other tests could be considered. Or multiple different tests could be used.

2) The second situation is where neither IHC or FISH deliver a clear positive or negative result, or if they give conflicting ("discordant") results.

3) Finally, if a tumor is designated HER2-negative but the disease is progressing faster than expected, then consider rechecking with another kind of test.

Agendia's TargetPrint test looks quantitatively at the amount of HER2 mRNA in tumor cells. This is different than standard IHC tests (like Dako's HercepTest) that look at the amount of protein on the tumor cell surface semi-quantitatively, or FISH tests (like Abbott's' PathVysion or Dako's HER2 FISH PharmDx) that look at the amount of DNA amplification.

Why might looking at mRNA be useful? Consider the biology. Within the cancer cells, a portion of chromosome 17 (home of the HER2 gene) is being amplified. Instead of the normal double helix of chromosome 17 DNA, the cell has aberrantly made many double helixes. There are too many HER2 genes so the cell naturally produces too much HER2 mRNA. These HER2 mRNAs float around the cell and are used to creates too many HER2 proteins.

In theory, the amount of DNA amplification, mRNA and protein should coincide. But biology is complex and scientists always have an imperfect picture of what's going on inside of the cell. In addition, there are strengths and weaknesses associated with different tests and lab techniques. Some tests are more subject to laboratory error, for example. So the idea of using different techniques to measure different aspects of biology (DNA, mRNA and proteins) and to cross check one against the other is a reasonable strategy.

In addition, analyzing mRNA as a means of understanding what's happening inside cancer cells has become important in recent years. mRNA analysis is the basis of Genomic Health's popular Oncotype Dx test and Agendia's better known test, MammaPrint test, both for assessing recurrence risk. So it is a growing diagnostic approach.

Back to TargetPrint. Yes, it analyzes HER2. But it also analyzes estrogen receptor (ER) and progesterone receptor (PR), also by looking at mRNA. Normally both are analyzed by IHC. Several recent studies show that ER testing is far from perfect. For example, a Yale study that just came out this week found that 10-20% of patients who are told they have ER-negative tumors really have ER-positive tumors. Another recent study found that patients test negative for ER by IHC more often on Fridays and Saturdays! So, as mentioned before, IHC is subject to lab and lab technician variability.

TargetPrint costs $1200 and it is covered by Medicare.