cutoff for her2

Hi Konakona:

Have you started trastuzumab (Herceptin)?

In another thread, you indicated:

"I just came back from my oncologist appointment and he told me I am her2 positive. I was equivocal at biopsy so they did a FISH test and it came back negative, also I had a mammaprint test done that said I was her2 negative. there were discrepancies about my ER status so he had the tumor retested her2 came back at positive 2.40."

It sounds like when the excised tumor was tested, you were advised that the result was considered "positive" by the expert pathologist. Is this correct?

What is considered "positive" differs according to the type of test performed. Regarding (F)ISH testing, there are two main types of ISH testing (single-probe versus dual-probe), and interpretation of the results differs.

Here is a simplified overview for information only regarding the various test results that are considered "positive".

http://www.asco.org/sites/new-www.asco.org/files/content-files/practice-and-guidelines/documents/2013-HER2-Algorithm.pdf

==> For Validated IHC assay, see Chart 2

==> For Validated single-probe ISH assay, see Chart 1

==> For Validated dual-probe ISH assay, see Chart 3. Note that with a dual-probe ISH assay, the HER2/CEP17 ratio is not the sole determinant. There are THREE kinds of results that are considered "positive" (see three yellow diamonds), considering also the "average HER2 copy number."

The above charts are taken from the 2013 ASCO Guideline, and additional explanations are provided under the figures in the original document:

2013 ASCO Guideline: http://jco.ascopubs.org/content/31/31/3997.full

If you are still wondering why there was a difference between the results of your testing on biopsy versus the results on surgery, it might be due to variability in performance of the assays, certain technical limitations with minimally-invasive biopsy, AND/OR due to "tumor heterogeneity." You may wish to ask your MO about these possibilities.

"Tumor heterogeneity" means there is some variation among different cells in the tumor, and can lead to different degrees of HER2 amplification seen between cells. The ASCO guidelines attempt to address non-uniform HER2 amplification, for example, by including consideration of average HER2 copy number per cell with dual-probe ISH.

HER2 testing based on biopsy is reliable for the purpose of neo-adjuvant (pre-surgery) treatment decisions. However, occasionally, there can be technical issues with minimally-invasive biopsy. See for example, this 2012 article. This document predates the 2013 guidelines, and may not reflect current practice in all aspects:

2012 article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503664/pdf/conc-19-315.pdf

In the 2012 article, see the discussion of potential artifacts and sample processing issues with minimally-invasive biopsy. Smaller tissue volumes might be less representative when heterogeneity is present. Note the comment that "[s]urgical excisions have long been the "gold standard" sample-type for the assessment of her2 status," which I take to mean that when available, the large amount of tissue and lack of edge artifacts and the like make surgical samples a preferred test sample.

The potential use of mRNA microarray technologies, such as BluePrint from the Agendia test suite that you had, that assess HER2 mRNA instead of HER2 DNA or protein are still being researched. The big clinical trials on HERCEPTIN used IHC and FISH to select patients suitable for treatment. The HER2 mRNA readout from the BluePrint test (Agendia) is still under investigation, and differences seen in your case and the studies as compared with (F)ISH could be explained by intratumor heterogeneity of HER2 status.

Please do not hesitate to ask your doctors to explain to you why in light of your various test results, you are considered HER2 "positive" to ensure that you receive current, accurate, case-specific, expert professional advice and that you understand your HER2 status and treatment recommendations.

I am a layperson with no medical training. The above is provided for information only, and is not a substitute for case-specific medical advice or determination by expert pathologist.

BarredOwl