Inconsistent test results

windingshores

I was geared up to do Taxol and Herceptin based on a positive FISH HER2 test on biopsy (IHC was equivocal), along with grade 3. Testing on my mastectomy specimens however were negative by dual ISH (again IHC equivocal). An Oncotype done on the biopsy specimen, without my knowledge, that was not in the record, was just discovered, and has HER2 negative. At this point my doctors are considering me HER2 negative but I have concerns.

I am ER/PR positive, 95% ER and 80% PR.

The other testing inconsistency is that the just-discovered Oncotype Dx done on the biopsy specimen shows a low recurrence score. The pathologist at the hospital that ordered it thinks this is weird, since my ki67 was high, grade there was 3, and I had lymphovascular invasion.

Pathology done on mastectomy specimens showed ki67 high at 20% (low end of high), grade 2/3, Her 2 1+/2+ on IHC and 1.2 on dual ISH (very different from the 2.1 obtained on the biopsy), mixed ductal and lobular in invasive part and CIS, DCIS with necrosis, lost e-cadherin in lobular parts, focal LVI.

For weeks since my mastectomy I have been told I would be doing Herceptin and Taxol then hormonal treatment. I have not had radiation though it was mentioned at a second opinion in passing, due to LVI, but they said 4/5 radiology onc.'s would not suggest it.

Due to the low Oncotype score, which I do not trust, I am now told that I will only do hormonal treatment. I want a new one done on the surgical specimen versus biopsy (which may have had more DCIS on slides, which could account for the lone HER2+). Does anyone else have highish grade, highish Ki67, and low Oncotype score.

I am not eager to do chemo, don't get me wrong. If anything I would be interested in Herceptin with the ambiguous HER2- I have read that it can be taken alone.

I have had two opinions (two hospitals in the same system) and my biopsy pathology was done in another hospital.

I am confused and still worried whether hormonal treatment is enough in the context of some of my test results, especially grade and ki67. I am also confused as to why the Oncotype of the biopsy material is determining treatment when the HER2+ from that sample is being discounted (with the explanation that the Oncotype has it as negative- wouldn't a FISH be more reliable? IF DCIS in the sample explains the HER2+ wouldn't it also affect Oncotype and make it lower?)

I know this is complicated and apologize if this is too much to post. If anyone else has had these inconsistencies would love to hear your treatment and outcome so far. Thank you!

NancyHB

windingshores,

You've really been through a lot of ups and downs lately. Making treatment decisions is challenging enough without inconsistent results on top of it all.

The Oncotype test is far different than pathology, but is considered reliable. The primary reason is how the sample is tested. Pathology looks at specific areas - hormone receptors, size, nuclear grade, etc. it doesn't often test for or take into account other components such as Ki-67 and genetic expression. This testing leads to a different, more comprehensive view of your specific cancer.

In my case my cancer "looked good" (my MO's words, not mine!) because it is Stage 1, grade 2, ER/PR+ and Her2- (equivocal until FISH testing). Because it was over 1cm they wanted to consider chemo and so sent off for Oncotype. My result - 42 - was a shock. Even more surprising is that my PR status changed to negative (it was <10% on pathology) and my ER was 6.6 on a scale where 6.5 is the cut-off for negative (my pathology showed <50% ER+). My Her2 - equivocal on pathology - was extremely negative on the Oncotype scale. My MO says I'm still considered ER+ but concedes my cancer likely acts more like TN. A year later my pathologist started routinely testing for Ki-67 so I asked for it; it came back at 50%, which supported even more the Oncotype results.

So, I can appreciate feeling like every piece of information you receive is different. It's frustrating and makes treatment decisions so much more difficult. I trust my Oncotype test because I felt I got more information than I had before, but I encourage you to keep asking questions until you get the answers you need.

*hug

NancyHB

And I spologize for multiple edits to the post above; I had to keep submitting it unfinished because the typing would slow and then freeze, and I didn't want to lose it

windingshores

Nancy, thank you so much. I have a call in to Genomic Health: they are really helpful on the phone. It seems that your ER- made your score higher and my 95% ER score made mine low. But I want to confirm that. I just found out that my second opinion hospital rated my tumor grade 3. So grade is different at all three places! I also found out that my primary hospital considers my LVI "focal" meaning one focus and most likely does not need radiation. And the surgeon just now agreed to take off my other one

I know I need to keep going and also feel I will know when to stop, which is soon. A conversation with Genomic Health, the biopsy pathologist, and my primary oncologist (in person, I don't want to do it on the phone) will finish this up. Hopefully it will just be hormonal treatment, but I need to feel safe as well as relieved.

I am so sorry about your surprise high Oncoscore! I see you did pretty thorough chemo and hope you are okay.

windingshores

I pressed this dilemma on my oncologist who asked pathology, and pathology said while the biopsy specimen was an "8" on the Oncotype, they estimate that the surgical specimen would be 13-18 (the cutoff being 18 for chemo consideration). Genomic Health will repeat with the surgical specimen and my health insurance will cover it.

I havae requested a second test with my surgical specimen. My oncologist is reluctant to order it but is checking with pathology to see if it is worthwhile in their opinion. My grade 3, LVI and 20% ki67 are persuasive. My 95% ER score may have lowered my Oncotype score somewhat but it is still hard to see how it could be only 8.

For anyone new, the Oncotype involves 16 genes plus 5 reference genes and measures distant recurrence risk. Genes include those related to proliferation, invasion, estrogen, progesterone, HER2.

I am 64 so maybe that is one reason all my docs are so resistant to reviewing this.

I did find out today that my second opinion doc is rechecking the HER2 by FISH since that was positive on biopsy and CISh was negative on surgical specimen.