Conflicting Dako and FISH results

I had a mastectomy approximately two months ago. When the Dako Hercept test first came back with a 3+ result, my oncologist suggested a TCH chemo regimen.  Right before beginning the chemo, the FISH result came back with a 1.3 - not amplified - result.  So everything is now on hold with the oncologist who said he has not encountered a Dako 3+ that came out not amplified in FISH ordering a third test, Oncotype DX.  

Is the FISH test more accurate than the Dako test?  I would like to think so to be spared the year-long Herceptin treatment.

Also, would the Oncotype DX settle the question one way or the other?  

Thanks for your help!

[Cleveland Clinic]

Dear cancer46: The role of Her-2 testing of breast cancer cells is to determine which women will derive benefit from the use of the drug Herceptin.  Herceptin binds to the “Her-2 Receptor” on the surface of cancer cells to cause cell death.  The chemotherapy Hercepin only works if the Her-2 receptors are present on the cell surface.  Imagine the receptor as a keyhole and Herceptin as the key.  Without a keyhole, the Heceptin cannot work.  

Unfortunately, the methods for predicting potential response to Herceptin (Daco/IHC, FISH etc) are imperfect.  The landmark studies that support the use of Hercepin in your situation chose women with Her-2 positive tumors as defined by Dako 3+ or FISH positive (greater than 2.2).  We are learning that some women with discordant results in Her-2 testing still benefit from Herceptin.  While FISH testing may be more “accurate”, there are studies suggesting women with Dako positive, but FISH negative tumors still benefit from Herceptin.  

There is no perfect method for predicting whether or not you will benefit from the added Herceptin.  However, based on your 3+ Dako testing, you would have been allowed to participate in the clinical trials that demonstrated women who received Herceptin lived longer.  

The Oncotye Dx test uses a THIRD method of measuring Her-2.  This test was not used in the landmark trials that support the use of Herceptin in your situation. Therefore, it is unclear how to apply the results of this test in estimating your chance of benefiting from Herceptin.

You may consider having your tumor examined by a pathologist at a large referral institution to ensure the testing was performed properly.

[dblwhammy]

I'd like to see an MD address your question.

From my own experience after double mastectomies my path report showed an overexpression of Her2/neu. The FISH came back in the low range. My oncologist wanted this double checked at a different lab to be sure, it also came back low. However, I decided to have the OncotypeDX evaluation as well. That test came back with a relatively high recurrance score so I decided to have chemotherapy as extra insurance. After finishing 4 cycles of cytoxan and taxotere 3 months ago, I'm taking Arimidex for 5 years and trying to keep my chin up!

[cancer46]

Thanks so much for your response!

I too am hoping that an MD from the Cleveland Clinic would answer my question.

Your message is encouraging; now I know I'm not the only one whose test results conflict.  When your oncologist ordered test from the second lab, was the Dako or the FISH test or both redone?  

My oncologist also suggested cytoxan and taxotere if the Oncotype DX score indicates a higher than acceptable risk for recurrence.  Do you mind telling me how high your score was for you and your oncologist to decide on 4 cycles of the TC regimen?  I'm afraid my oncologist would come back with a recommendation of 6 cycles when 4 would be sufficient.

Let's keep in touch.  You could probably tell me much about your TC experience that would help me weather my trials.

Yes do keep your chin up since the worse is over!

[dblwhammy]

Hi -

I'll post to your inbox to keep the forum from what may be considered clutter.

dblwhammy

[lizziecee]

Apologies for butting in here....can you explain how to post to a private inbox on this forum please?
Many thanks,
Liz.

[cancer46]

Thank you very much for your illuminating response.

I tried looking up the studies you referred to which report FISH negative tumors benefit from Herceptin.  However, all I could locate are the brief and tantalizing write-ups of how the FISH ratio does not reflect increased chromosome 17 polysomy and the Her2/cen17 may not be the best indicator of Her2 status in such cases.  But these studies were done on metastasized breast cancer patients.  Are there studies of such benefits for adjuvant treatment?  Would appreciate your giving me the citations so I could look up the articles.

I'm not sure my oncologist would agree to sending the tumor samples to a large referral institution again for FISH testing because of the cost involved and my insurance may not pay for it.  In any case it appears from the studies mentioned above, it's not the accuracy that matters so much as whether both Her2 and cen17 are high to yield a low FISH ratio.

In addition, is a blood test for CTCs, tumor cells in the bloodstream, an expensive one.  Depending on the cost, I'll either ask my oncologist to have it done or try to have that test in a laboratory where I can pay for it myself.

I have an appointment with my oncologist next Wednesday and would greatly appreciate answers before then.