New Here with Her2 Questions

[Yorkiegirl]

Moving this question to this board to see if any one can answer. This was on the Herceptin/Ty baord


#1 Linda G.
Junior Member

Join Date: Oct 2008
Posts: 1


New Here with Her2 Questions
This is my first post here after finding your site after watching the Lifetime movie Living Proof. I'm 60 and ER+, node negative. I was diagnosed and had bilateral mastectomy in 1999, CMF, and Tamoxifen 5 years. To date I'm NED. In a couple weeks I'm having a chest CT due to some on and off pain and since I've had no chest x-ray for 5 years my oncologist felt it would be wise and more thorough than just an xray.
My pathology said my HER2 status was "mildly positive." My full report is at home and I live out of town all summer so it's not handy to verify other details right now. What actually determines how Herceptin will work for a patient? Are there varying levels of Her2 positive? I've noticed some people say they are Her2+++ for example. I'm assuming the more positive you are the better the drug might work or is it some other score they look at? Sorry if I've posted this on the wrong forum.

Thanks,
Linda G.

[dlaxague]

Linda asks: Are there varying levels of Her2 positive?

Yes. There are at least two different ways to test for HER2. IHC is considered less accurate, and gives a result in pluses - one +, two + (++), three + (+++). FISH is another assay and its results are considered more accurate and usually the result is returned in a number (that is actually a ratio but is usually just stated as one number). Two and greater has been the standard for positive but they are now looking at lower levels for response to Herceptin.

Linda again: I'm assuming the more positive you are the better the drug might work or is it some other score they look at?

This is the interesting part. No, there does not appear to be any relation between response to Herceptin and degree of HER2neu positivity. About half of all HER2+ cancer responds to Herceptin and as far as I know, we are not close to figuring out how to know who is who, ahead of time.

To link to the topoIIa thread: I asked on the webinar that Dennis Slamon did for the LEADers list if topoIIa status seemed to be related to FISH score (higher FISH, more likely to be topoIIa +?) and he said they had looked at this and the answer is "no".

Debbie Laxague

[dlaxague]

The other piece of the Herceptin response/level of FISH question is "do those who have a higher FISH ratio tend to have worse outcomes (does higher score = more aggressive disease?)".

If you know the answer, do you have references to share?

Thanks,
Debbie again

[Lien]

Don't know about that, but I did find an abstract about research on her2 and surgery. I can't access the article and have no idea whether this research has significance, but it's an interesting angle.

http://linkinghub.elsevier.com/retri...59804906001535

Jacqueline

[Lien]

And I found something on FISH scores predicting response to Herceptin. The study is relatively small, so I don't know how valuable this info is.

http://www.medicalnewstoday.com/articles/92013.php

Jacqueline

[dlaxague]

Hi, that's the first I've heard of that. It makes sense but I thought that studies had showed no correlation. Is my memory failing me on this also (sigh)? Although it is a very small study - actually only 77 were FISH +. I went looking for full text without success but I did find an abstract that had some more numbers (copied below). I wonder many things but first - what was the cut-off used for low vs. high expression? Anyone have access?

Other questions would be whether neoadjuvant studies and short-term information like PCR are useful for predicting longterm stats (answer unknown at this point, as far as I know).

I think that most of the previous information about this came from researchers trying to decide what to use as the cut-off for HER2+ with FISH?
Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification.

Arnould L, Arveux P, Couturier J, Gelly-Marty M, Loustalot C, Ettore F, Sagan C, Antoine M, Penault-Llorca F, Vasseur B, Fumoleau P, Coudert BP.
CLCC G-F Leclerc and 1FR100, Dijon, France. larnould@dijon.fnclcc.fr
PURPOSE: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer. EXPERIMENTAL DESIGN: Breast biopsies from 93 HER-2-positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+. RESULTS: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors. CONCLUSIONS: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.

[Linda G.]

Thanks Vicki for putting my post on this forum. I am so impressed with the feedback- I've learned a lot already on this forum. Did not know about FISH or IHC ways of testing nor had I ever heard of topoII. Much appreciation to you all.

[dlaxague]

Sorry, Linda, we kind of took over your thread with more complicated things than you were probably looking for.

I did find a few references that say they could not find a relation between Herceptin response and benefit from Herceptin:

Dr. Worta McCaskill-Stevens (National Cancer Institute, Bethesda, Maryland, USA) presented new data from the HERceptin Adjuvant (HERA) trial showing that the level of HER2 amplification does not predict if a patient will derive any disease-free survival (DFS) benefit from treatment with trastuzumab. McCaskill-Stevens' co-investigators found no significant interaction between HER2 amplification determined by central fluorescence in situ hybridization (FISH) testing and the relative DFS benefit of trastuzumab.
http://tinyurl.com/62adc2

"Patient and disease characteristics are presented in Table 1. Twenty-nine patients (64%) achieved pCR after 24 weeks of preoperative therapy. Age, nuclear grade, tumor size, nodal status, clinical ER status, and HER-2 gene amplification level, as detected by FISH, showed no significant association with pCR in either univariate or multivariate logistic regression analyses."
(small neoadjuvant study):
http://tinyurl.com/5rwhws

So once again, it appears that the answer may be - no answer (yet).
Debbie Laxague

[Linda G.]

Debbie,

No need to appologize. I'm always up for learning new things, it's the remembering part I have trouble with!
Another thing I'm wondering- since my diagnosis and CMF treatment was almost 10 years ago are they now giving Herceptin right off the bat to newly diagnosed folks who are Her2+? Back then they just told me if I had a reccurance Herceptin might be an option.

[dlaxague]

Linda G said: Another thing I'm wondering- since my diagnosis and CMF treatment was almost 10 years ago are they now giving Herceptin right off the bat to newly diagnosed folks who are Her2+?

Yes, Linda, they are. The adjuvant Herceptin studies are showing about a 50% decrease in recurrence, so far. The debates about this right now include what is/are the best chemo(s) to give it with (either concurrently or sequentially), what is the best length of time to give it, and when it's best to give it before surgery as opposed to only after surgery. Plus there's at least one study that showed benefit from Herceptin for cancers that tested below the cut-off for HER2 positivity so that has raised questions there.

Debbie Laxague