Positive or Negative???

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KEW
KEW Member Posts: 745

Hi,

Here is my story.  See my sig line and you will get the gist of my dx. Her 2/neg.  Well, in April of 2009 I went to talk with another oncologist, just because I heard he was great and I wanted more information.  Since I had two tumors that the original pathologist counted as one the onc I was getting an opinion from ordered both tumors to be examined, since one of them never was.  He called me and told me it was the same, not to worry.

I just got all of my medical records and it turns out that the path done in April of 09, came back the same for ER/PR, my mib-1 was now intermediate, FISH still negative, but the immunohistochemical test (the one that gives 1+, etc) went from 1+ to 3+ suddenly by that test I'm positive according to the dictation.  My onc and the opinion onc didn't say a word to me.  I called my onc on Friday asking about this and then sent him an email with all the information and I haven't heard a word.  My core biopsy was used to determine my original results and they were not redone when I  had my BLM, but of course they did all the other path things with my breast tissue.  When the path was redone in April about 6 months after BLM they used the breast tumors/tissue collected at BLM.  How can there be such a difference?  Have I been positive all this time and nobody picked up on it?  If anyone has any information about the tests I would appreciate it.

KEW

Comments

  • kittycat
    kittycat Member Posts: 2,144
    edited May 2010

    I was told that I was triple negative.  Then, I got my path report.  It says the HER2 scored a 2, weakly positive.  Huh????

  • Lilah
    Lilah Member Posts: 4,898
    edited May 2010

    Hi KEW and Kitty -- I saw your posts here and wanted to say hi.  I actually don't have answers for you, Kew, but am curious to see what people who know have to say.  Were you given a path report on your actual breast tissue at time of BMX?  (Sorry there's a lot to follow here).  Your original diagnosis was based on a core biopsy... which is a smaller sample.  What seems odd is that you even went to the trouble of getting a second opinion on the pathology in April 09 and still no one said anything.  It may have to do with the FISH report, though, which not everyone gets and which gives more/finer detail/info than plain old HER2 test (if I remember right).  Sorry I can't be more helpful.  I'll mark this thread though and keep up.

  • TriciaK
    TriciaK Member Posts: 362
    edited May 2010

    I'm no expert on this despite being highly triple pos myself!!  However if the IHC test came back 3* that means highly her2+ pos so you really should be having herceptin to add to your chances of not recurring.

    Try posting this on www.her2support.org where you'll get many answer's and an explanation!!!

    I can't believe neither of these onc's came back to you sooner with a reply and makes me think they made a mistake somewhere.  if you really are her2+ you need to have herceptin so ensure you do whatever you have to in order to get that!!!

    Tricia xx

  • lovetosail
    lovetosail Member Posts: 544
    edited June 2010

    Hi - this is a complicated issue.  FISH is more accurate than IHC.  However, false positives and negatives can occur.  I was 1+ on IHC and a ratio of >5 on FISH, so HER2- by IHC and HER2+ by FISH.  My onc (who is part of Dennis Slamon's research team, so they know their stuff wrt HER2) treated me as HER2+ and I went in clinical trial, receiving neoadjuvant TCH+Tykerb.  I had several additional core biopsies as part of trial protocol, and FISH was done on those samples and I was HER2+ on those as well. 

    Originally my tumor was ~2.2x2.5x1.5 or so cm on MRI.  The path report from my MX showed that >80% of the original was now gone, what remained had isolated patches of tumor, none greater than 4mm in size.  The cancer cells that remained were damaged by chemo.  But what is interesting is that the cancer that remained was HER2-.  So my tumor was heterogeneous wrt HER2 status, and it is becoming more widely accepted that this is possible.  Maybe that is going on with you as well, or maybe you had false positive or negative (depending on which you believe) findings.

    I'm very happy my initial core biopsy FISH results were from one of the HER2 + sections of the tumor - this meant I got Herceptin right away.  Like Tricia says, you definitely want Herceptin if any of your tumor is HER2+

    Good luck!!!

  • Drim
    Drim Member Posts: 302
    edited June 2010

    Hi KEW - I had a HER2 issue as well. My core biopsy came back equivocal so they sent it out for FISH. When I decided to go with my 2nd opinion BS she realized that they had never completed the FISH study and requested it again. Then I had my lumpectomy and when I met her for the follow up she told me the FISH came back highly positive - 4.5. I was shocked.

    I decided that since there was such a delay with the FISH that I would request them to test the lumpectomy tumor. I found the results of that when I went for my ONC appt. - 1.6. The doctor was quite surprised by this but what she told me was that it was unsual to retest. Once the biopsy comes back positive they don't retest.

    What ended up happening is that they sent my tumor out for lots of tests - apparently they disected the heck out of it and what they found is, just like lovetosail, is that the tumor was heterogeneous.

    It is a little disturbing to me that now that they have all of these treatments, that the tumor isn't inspected more carefully to find out all of its charactaristics. What if my core biopsy had come back negative. Then I would never have known I was HER2+. SCARY! I'm sure it's expensive to do more lab testing and then to do lots of treatment but it's got to be more expensive to treat metastatic cancer. 

    I also see that your Oncotype score is 15. My was 19. Oncotype also had me as HER2-. Now I feel like that test isn't as reliable with a heterogeneous tumor.

    I hope all the best for you!!!

  • lovetosail
    lovetosail Member Posts: 544
    edited June 2010

    Hey Drim - interesting story - so glad you got the HER2+ portion sampled and are getting the appropriate tx!

  • Estepp
    Estepp Member Posts: 6,416
    edited June 2010

    Karen.. I am NO expert.. but I was told If the test came back under 3 ( I think I am remembering this right) then I was not considered her2. 3+.... was.

    This is why you see the term.....Her2+++ a lot out there on the internet.. ( 3+)

    Now, this was two yrs ago.. things might have changed.

    I would think you could ask any other oncologist if the test was 1 or 2, should you have had Herceptin.

    xxxooo

  • coss
    coss Member Posts: 48
    edited June 2010

    My core biopsy was 1+ on IHC, but sent for FISH testing by the pathologist.  Good thing.  It came back 6.1, definitely positive.  I was shocked.  One minute I was wondering if I could avoid chemo and the next it was ACT and a year of Herceptin.  How many pathologists report IHC1+ as negative and let it go at that?  I feel like I dodged a bullet. 

  • lovetosail
    lovetosail Member Posts: 544
    edited June 2010

    Coss - I know!  I feel the same way.  My onc told me that UCLA routinely does FISH on all samples, regardless of IHC result, and ~3% of IHC 1+ are strongly positive (high ratio) with FISH.

  • lana12
    lana12 Member Posts: 3
    edited June 2010

    Hi I am new to these boards and have so much confusion.  My pathology came back as ER + and PR + and HER2+1.  Do you all think that the FISH is a more reliable source than the IHC?  I have no node involvement and was really hoping to avoid Chemo.  I want to do the right treatment.  I am 45 and premenopausal. 

  • lovetosail
    lovetosail Member Posts: 544
    edited June 2010

    lana12, ask your doctor if they are following up the IHC with FISH.  I believe that FISH is considered to be more of a gold standard than IHC.  A lot of places don't.  IMHO, if you have a FISH result that suggests HER2+, it is in your best interest to get Herceptin, regardless of the IHC result, but your oncologist is certainly way wiser than I am in this regard!

  • orange1
    orange1 Member Posts: 930
    edited June 2010

    The "standard of care" is to send IHC 2+ tumors out for FISH testing, and call IHC 1+ tumors "negative"  However, as lovetosail points out, occasionally IHC 1+ tumors turn out to be positive.  If your tumor is in fact positive, then you are at much higher risk of early recurrence, but will not get the chemo/herceptin that would greatly reduce that risk.

    Also, I saw from your previous post that you had multiple tumors in one breast.  Multiple tumors are especially common in Her2+ cancer.

    If it were me, I would have the tumor sent out for FISH testing even if only IHC 1+, even if I had to pay for it myself.

  • Caya
    Caya Member Posts: 971
    edited June 2010

    My tumour was sent out to three different labs, because the original IHC score came back as Her2+++, but also highly ER+/PR+ and had a mucinous characteristic,- which is good, but very rare (only 2-3% of BC tumours are mucinous).  Unheard of to be mucinous and Her2+ - my onc. could not believe it and finally the FISH test confirmed my Her2+ status. I'm just an original, I guess...

    I also had 2 tumours in my breast - 1.7 cm. and 1.0 cm. 

    Please KEW insist on getting the FISH test - and discuss with your onc. about getting Herceptin.

  • orange1
    orange1 Member Posts: 930
    edited June 2010

    Lana- 

    I neglected to answer your question. Yes, FISH testing is more reliable than IHC testing.  IHC testing for Her2+ is very sensitive to sample hold time before preparation, sample preparation itself and is somewhat subjective.  

    I was IHC 2+, but had greater than 10 gene copies - a very highly positive result.  I also had multiple tumors. 

  • orange1
    orange1 Member Posts: 930
    edited June 2010
     In this study - all classes of tumors that showed evidence of Her positivity (IHC 1+, 2+ 3+ and FISH+) benefited significantly from Herceptin, including tumors that scored IHC 1+ or 2+ and did not subsequently test positive by FISH testing. From Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post Meeting Edition).  Vol 25, No 18S (June 20 Supplement), 2007: 511AbstractBenefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors:  Central testing results from NSABP B-31S. Pal, C. Kim...others511Background: Trastuzumab is a humanized monoclonal antibody targeted to HER2 protein and currently indicated for Her2 positive breast cancer defined by overexpression of Her2 protein (3+ IHC staining by HercepTest) or Her2 gene amplification (Her2/CEP17 ratio over 2 by PathVysion FISH assay).  These criteria were determined for advanced disease but have not been formally tested in the adjuvant setting.  We examined these tests' ability to predict benefit from adjuvant trastuzumab in NSABP B-31.  METHODS:  All available tumor tissue blocks from the B-31 trial were sujected to HercepTest and PathVysion assay as defined in the B-31 protocol.  Formal statistical test of interaction between HER2 levels measured by these two tests and benefit from trastuzumab was performed.  RESULTS: 207 or 1795 cases (11.5%) showed gene amplificiation as as determined by PathVysion, and 255 of 1662 (15.3%) showed overepression as determined by HercepTest.  161 of 1662 (9.7%) had neither gene amplificiation nor overexpression  There was a consistent benefit from trastuzumab in every subset defined by IHC or FISH.  No statistical interaction was found between DFS benefit from trastuzumab and level of protein (p = 0.26) or Her 2 gene copy number (p=  0.60).  Benefit was observed in patients with tumors that were negative for FISH and had less than 3+ staining intensity on IHC by HercepTest (RR= 0.36, p = 0.32).  CONCLUSION:  Current definition of HER2 overexpression/gene amplificiation based on data from adjvanced disease may need to modified for the adjuvant setting.In all categories of Her2+, regardless of degree or how measured, relative risk with Herceptin was less than half of what it was without.  And all results were highly statistically significant, meaning results were likely not due to random chance. 

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