Oncotype dx for HER2 Positive?

webu · January 2011

I'm confused. Everything I have read has lead me to believe there it would be pointless to do the oncotype dx because I am HER2+++ and would need chemo no matter what. I had the FSH test, which I thought was definitive. My BS did not order the oncotype initially, and my onc didn't think it was necessary, but then I went for second opinion to an onc who is one of the top specialists in HER2+++. She said she thought that my tumor wasn't acting like it was HER2+++ because it was slow growing and strongly estrogen and progesterone positive. She recommended that I get the oncotype dx before starting chemo. I got it (although it will be a fight to get my insurance to pay for it). My onc (the original one) called me with the results yesterday, and it does still show that I am HER2 positive, although not as strongly as the FISH test showed. My score was 34, which was not surprising.

My onc is going to confer with the specialist on whether we should still go with the current treatment plan (TCH 4 to 6 tx followed by radiation and then either tamoxifen or an aromatase inhibitor), or if these results change anything.

Did any of you other HER2+++ ladies have the oncotype dx, and did it change your treatment in any way?

lago · January 2011

No but I am strongly HER2+, very fast growing and 30% ER+, 5% PR+ And the onc specialist you speak of is my onc as you know. She did not order the test.

The studies so far show that Herceptin works better with chemo. I would think if you are getting Herceptin, regardless of what the onc test says that they would recommend chemo.

I am having 6tx of THC (one more to go) then finish the year with Herceptin and aromatase inhibitor (in chemopause right now).

-----------------------------------

I know this is confusing but it is good they are checking. This might be less confusing once the test comes back.

Letlet · January 2011

I am stage II as well, my tumor was around 3.7. My breast surgeon pretty much told me gently that I did not need the oncoype test because based on my pathology from the surgery I would definitely need chemo. Not sure if the same would be said for a 2 cm tumor. Just curious why you are getting radiation with 0 positive nodes. Is it because you had a lumpectomy?

webu · January 2011

lago - Dr. C also recommended going right to an aromatase inhibitor instead of tamoxifen, even though I am currently premenapausal. My other onc had recommended two years of tamoxifen first. Dr. C said that as long as my hormone levels were carefully monitored, the aromatase inhibitor would be just as effective and have fewer SE's than tamoxifen. I am 50, so I would have gone through menapause sometime in the next few years.

Letlet - yes, I did have a lumpectomy.

lago · January 2011

Webu she said the same thing to me. I'm now in chemopause… and turn 50 at the begining of February. Tamoxifen doesn't always work well on HER2+ and there are some more serious SE than with aromatase inhibitor. But the later can have issue with osteoporosis. The later is supposed to work a little bit better than Tamoxifen.

So ya I will be starting generic arimidex after I finish chemo. Next time you are in Chicago we should meet!

swimangel72 · January 2011

Hi webu - my treatment plan was changed by the results of my FISH test - not the Oncotype DX. My breast surgeon ordered the Oncotype DX for me before the FISH test was ordered. (My insurance company paid for both.) My score came in at 22 (low-intermediate) and I went with a uni-mx with immediate Diep recon.........it was only after recovering from surgery and my first visit with an Onc (a big mistake not to see a medical Oncologist before deciding on surgery) - and at first he said all I would need would be Arimidex, and he wrote me a prescription and was about to send me home, when he took another look at my paperwork and said, "Wait, what's this? We never received the results of your Fish test. Wait a few more minutes......" and 15 minutes later, he came back with a sad face and told me the tumor was Her2+ and I would need chemo and Herceptin. So I felt the rug pulled out from under me yet again.........but in retrospect, I'm happy I went through the chemo especially since an Oncotype score of 22 is NOT that reassuing even if the tumor was Her2 negative. My onc gave me 4 months of Navelbine every two weeks with Herceptin (which continued for the year). It was an unusual protocol, but I had 3 other oncs agree with him and he didn't want me to suffer the SEs from stronger chemo drugs. It's nearly three years since my original dx and I'm doing very well - the joints bother me when the weather changes since I'm still on Arimidex - but I'm so happy that's my only complaint.

TriciaK · January 2011

I think an onco test is not worthwhile if her2+ as it always comes back with a very high score indicating chemo is needed!

Tricia x

worldwatcher · February 2011

I just got my Oncotype score of 26, 17% (within the "gray" Oncotype area of under 31) recurrance score, but the shocker is that my HER2 score is 10.7, just barely into the "equivocal" zone and within the deviation number of .5 between the negative and equivocal zones. The FISH score had me as a positive, the IHC score was equivocal.

That was good news for me since I don't plan to do chemo and my Onc with 35 years of practice has had very good luck with Tamoxifen.

IowaSue45 · February 2011

Ladies I have a question, are there different levels of being her2neu? Or is it you either her2neu or not? I guess I never thought of it before because I thought you either are or not. Until I saw lagos comment that she is strongly her2neu. I pulled out my pathology report and was trying to figure out if I am highly her2neu. I remember my onc. saying at some point that I didn't need a oncotype because I was defiantly her2neu. So is there any score on your path. report? I can see on mine where it has her2neu poss. + 4, idk what that means, way positive I guess.

Worldwatcher where do you get mitolic score 1? Mine says high.

Drim · February 2011

webu - I am HER2+ and ended up with the Oncotype test. That is because I was getting a lot of conflicted results from the IHC and FISH studies. biopsy IHC = equivocal, biopsy FISH = pretty highly positive, surgery tumor FISH = negative. So with that my med onc gave the okay for the Oncotype Dx (which insurance paid for). I ended up with a score of 19 but my onc and 2nd opinion onc. were not convinced I was HER2- even though that's what the Oncotype test said.

One of the oncs described it like this - the tumor section that was sent gets mixed up in a 'blender' and then tested. They say my tumor was heterogeneous (some parts HER2+ and some HER2-) so he felt like the sample was like an average. At the end they declared me HER2+ so I needed the chemo and herceptin, BUT, due to the low onco score my onc. switched from TCH x 6 to taxotere/cytoxan x 4 with the H of course.

TriciaK · February 2011

Iowa Sue, yes, there are different scores and it sounds like you're highly her2+ as I am!!!

Usually if there's a conflict with the testing the herceptin is done which has made such a difference to our type of bc:)

Worldwatcher, maybe you could do herceptin without the chemo?

Tricia x

dancetrancer · February 2012

Timely, interesting thread for me. I have a very small t1A (3 mm) HER2+ tumor. It is controversial over whether chemo/Herceptin is indicated or not. First onc from large institution said no treatment (other than Tamoxifen) is needed. I was also told my tumor is too small to run the oncotype. Just saw 2nd onc today, and he strongly recommends chemo/Herceptin or Herceptin only at a minimum. He wants to try to run the oncotype which I am all for, if it makes a difference...but again, I was told HER2 trumps any oncotype. What I don't understand is if they aren't sure about these small HER2's, and there is such controversy, why don't they always run the onco to figure it out...so it makes me wonder if the onco is reliable for very small tumors, since this apparently is not routinely done. Thoughts, anyone?

suzieq60 · February 2012

I did some reading up on the onctotype test and found that all it does for HER2 is confirm that it is HER2 and that was all the test could do.

dancetrancer · February 2012

Interesting susieq. Did you save any of your references/links that you could share?

suzieq60 · February 2012

I'd have to google it again. I'll see if I can find it for you

dancetrancer · February 2012

Thanks susie. Of course you know I'm googling, too. :-) Will share anything definitive I find.

suzieq60 · February 2012

Found this so far - very interesting - not what I was looking for but scary :

http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=82476

Can't getthis link to go to the study - maybe you can use the study id to find it or google "oncotype dx testing HER2"

suzieq60 · February 2012

And this:

http://onlinelibrary.wiley.com/doi/10.3322/caac.21133/full

Interesting final statement - the Oncotype DX HER2 assay was not developed, validated, or approved as a predictive test to determine which patients should receive anti-HER2 therapies

suzieq60 · February 2012

http://www.labtestconsult.com/absent-gold-standard-for-her2-testing-researchers-question-role-of-oncotype-dx-beyond-ihcfish/

Sorry about the first link - it doesn't seem to go to the correct study and I couldn't edit it, but this one tells all

suzieq60 · February 2012

I was doing my searches 2 years ago, but these new articles are very revealing.

cbm · February 2012

I just requested an oncotype test on my tumor sample from 2008 mastectomy. I already had ACTH, a second year of herceptin, and a year in the Neratinib trial. However, I had a mixed tumor, and my oncologist and I have an ongoing discussion about how long I will need to be on Femara.

I had a 1.6 cm IDC/DCIS/ILC/LCIS combo (Grade 2) with what I believe is a fairly low Her2/Cep 17 ratio of 2.4. Not that I know what that means, exactly.

I asked for the oncotype test because it had never been done, and I want to know the score for future reference. I was under the impression that the oncotype generally suggests the recurrence risk and thus the need for chemo, and that with HER2 the risk is particularly high, so chemo is a given. My oncologist ordered the test, and said he didn't realize it had not been done before.

Warmly,

Cathy

dancetrancer · February 2012

Thanks Susie. If you read the information prior to the final statement:

No guidelines state that HER2 status as reported by RT-PCR should be used to determine HER2 positivity, nor does Genomic Health state or promote the use of their results to determine if a patient should receive anti-HER2 therapy. It is feasible, however, that clinicians may consider the HER2 results from the Oncotype DX in their clinical decisions regarding anti-HER2 therapy. The findings of this study support the ASCO/CAP recommendation that clinicians should use IHC/FISH or FISH alone to determine HER2 status.

"Our study on HER2 discordance highlights the fact that one test cannot provide all the answers [regarding optimal treatment for women with breast cancer]. The oncology community needs to continue using the validated HER2 assays in clinical treatment decisions and reexamine their overreliance on the Oncotype DX test," Dr. Bhargava says.

Dr. Hayes agrees, noting that the Oncotype DX HER2 assay was not developed, validated, or approved as a predictive test to determine which patients should receive anti-HER2 therapies.

I think all this study is saying is that the Oncotype isn't reliable to tell you if you are HER2+ or not. That's not what I am interested in confirming - I know I'm fully positive (3+, FISH 9.2 when anything over 2.2 is positive). I'm wondering if the distant recurrence score is predictive for me or not. I just called Oncotype, the representative said certainly it is up to the oncologist to decide, but reiterated that onco is predictive independent of the tumor size, grade, and age of the patient, b/c all it looks at is the biology of the tumor. Well...HER2 is the biology of the tumor, and one doc tells me it's important, the other one says it isn't when your tumor is as small as mine. I'm talking in circles, hope this makes sense. I still have no major points to make except to say don't trust the HER2 component of the Oncotest.

And for anyone HER2+ thinking of getting this done, make sure you doc orders a benefits investigation where Onco has to call you prior to the test being billed and tells you what coverage level to expect. This way, you are more protected if it eventually is denied. I was told Onco will not bill you for more than what they tell you when you receive that call from them.

suzieq60 · February 2012

I was reading about it when I was diagnosed in 2009 as we don't have the test available here. What worries me, is what if this test is proven to be inaccurate in the future and that many women (not HER2) have relied on it to decide treatment - that's something that is quite possible.

LilliM · February 2012

Dancer:
You asked an excellent question. Is the Oncotype DX Recurrence Score predictive of distant recurrence regardless of factors such as HER2 status or size of the tumor? There appears to be a lot of confusion among doctors about the nature of Oncotype DX. It's a paradigm shift from the way tumors have traditionally been evaluated, and I suspect many professionals advising patients haven't made the shift.

My first RO is a case in point. He told me that, based on my pathology report, staging of my tumor, size, grade, etc., chemo was indicated, no question about it. Furthermore, he was fairly certain my Oncotype DX Recurrence Score would come back in the high intermediate to high range reflecting the conclusions he had drawn from my pathology report. As it turned out, my Oncotype DX Recurrence Score was 18, low enough for me to make a reasonably confident decision to forego chemo.

In my case, the "biology of my tumor" said something distinctly different from what traditional staging, and my RO, would have otherwise led me to believe.
Lilli

dancetrancer · February 2012

Lilli, thanks for sharing your story! And nice to hear from you again. I need to get back to the other boards and say hello to everyone, but I've been a bit wrapped up, LOL.

So, I've been doing my usual digging into studies...check out what I found on this topic:

Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature

This study talks about the oncotype and also about the mammaprint (70 gene-signature) gene test. I found the results/discussion fascinating. It think it explains why we've heard so much that a HER2+ test trumps an Oncotest. It also indicates that a mammaprint test may help actually stratify out which HER2 tumors are lower vs higher risk. I'm going to paste the last part of the discussion in full...I'm thinking of asking my doc to what he thinks of running the mammaprint test instead of the oncotype, but I still need to read more before I open my mouth and possibly insert foot (I'm good at doing that and annoying docs!).

"The second widely used prognostic tool is the 21-gene recurrence score (Oncotype DX, Genomic Health Inc., Redwood City, CA, USA; Paik et al, 2004), which is based on real-time RT-PCR and uses formalin-fixed, paraffin-embedded tissue, and is retrospectively validated for ER-positive breast cancer. As the measurement of the expression of the HER-2 gene itself was chosen as important contributing factor in this ‘knowledge-driven approach', most if not all HER-2-positive tumours are classified as intermediate or high risk and therefore, this assay is unlikely to add prognostic information for HER-2-positive disease. Of the 55 HER-2-positive cases identified in the NSABP B-14 trial, 50 had a high recurrence score (RS) and 5 had an intermediate RS, respectively, whereas none of the patients was assigned to a low recurrence score (Paik et al, 2004; S Paik, personal communication). In comparison, the 70-gene signature was developed using the ‘data-driven approach' with unbiased, genome-wide gene expression. The HER-2 gene itself was not on the list of the 70 priority genes selected solely on the basis of differences in gene expression levels from intact RNA of frozen tumours. This study suggests, that a clinically meaningful and larger proportion (22%) of chemotherapy-untreated HER-2-positive tumours are identified as low risk by the 70-gene profile, and these patients experience a favourable long-term outcome. This is especially remarkable, as 13 of 16 ER-positive low-risk patients did not receive endocrine treatment at the time the original studies have been conducted.

Avoiding overtreatment with chemotherapy and/or trastuzumab for truly low-risk HER-2-positive patients is an important goal, taking into account the risk of serious adverse events and the cost of these treatment regimens. Currently, trastuzumab monotherapy in the absence of chemotherapy is not regarded as standard of care for patients with HER-2-positive disease, although many experts at the St. Gallen consensus conference believed that trastuzumab alone may be reasonable for a subset of patients with HER-2-positive disease in the future (Goldhirsch et al, 2007). Our data raises the intriguing hypothesis that this strategy of anti-HER-2 therapy in combination with endocrine therapy might first be tested in patients with highly endocrine-responsive HER-2-positive disease and/or patients with hormonal receptor expression with a ‘good prognosis' 70-gene profile. Recently, Chia et al (2008) reported similar findings, as the HER-2-positive, ER-positive subgroup of T1 cancers had a more favourable outcome with a 10-year BCSS of 92%, as compared with the HER-2-positive, ER-negative subgroup with a 10-year BCSS of only 76%.

In summary, our study suggests the existence of a low-risk HER-2-positive subgroup of patients with favourable outcome, which can be identified by the 70-gene MammaPrint gene signature. The results of this study support the evaluation of less intensive treatment strategies in this low-risk group. Further validation of this important finding is ongoing in the MINDACT trial, whereby patients with HER-2-positive disease deemed to be at a high clinical risk by Adjuvant!Online (Ravdin et al, 2001) with a ‘good prognosis' MammaPrint profile may be randomised to receive no chemotherapy but may be treated with trastuzumab alone at the discretion of the treating physician."

cbm · February 2012

Thank you dancetrancer; I did ask the doctor for benefits confirmation. I think it's unlikely it will be approved, but I will try.

Warmly,

Cathy

bucky317 · February 2012

dancetracer Hi there, I have been following your story and it this must be driving you Crazy!!! (Not knowing chemo or no chemo) I was Her2 negative by FISH on biopsy.(score was 1.2) and I had a ONCOTYPE DX test done to see whether I needed chemo or not. It came back high @ 28 and EQUIVOCABLE @ 11 for Her 2. I was so confused as to what that meant. Am I positive or negative?!!! What does this mean!! Chemo was in the cards for me because of my score, but my case was discussed by the Cancer Committee at the hospital, to discuss the need for Herceptin (or not) They repeated the Her 2 test by IHC and it came back positive! Herceptin it is!!! I did 4 treatments of Taxotere and Cytoxan with Herceptin. I would of had 6 treatments if my ONCOTYPE score came back over 40 or 49. (can't remember, chemo brain Undecided ) My MO , like fluffqueen's and so many others' told me that there are not enough successfull studies done with Herceptin to have it alone, BUT, he believes that in the near future that it will be able to be given alone with chemo and for 6 months instead of the one year plan.

Your tumor is so tiny. Heres hoping and praying for a low recurrance score for you Smile

dancetrancer · February 2012

Thanks Bucky, yes this is making me completely wacko!! Wow what a crazy story you had there, too. What the what? How confusing!!!

bucky317 · February 2012

dancetrance I just read my post and I meant that my MO told me that Herceptin w/o CHEMO will be more widely used and for less duration. Hope I didn't confuse you more!

dancetrancer · February 2012

LOL, Bucky, that is so funny - I didn't even catch it! It's like those tricky word games you see posted on facebook. Your mind reads what it wants to believe!

cbm · March 2012

I just wanted to follow up on my posting of February 8. I was diagnosed in 08 (St 2 Gr 2, ER/PR/Her2+, with one node) and had two years of Herceptin and a year in the Neratinib trial. I asked my doctor about the Oncotype test and he ordered it, as we have been going around and around about the Femara in my future; I'm coming up on four years.

I got a recurrence score of 9. Though I'm aware that the Her2 portion of this test is not trusted by many medical oncologists, this test says I'm Her2 negative, not positive, though close to the threshold.

I don't have strong feelings about having gone through all that treatment; the test wasn't available for node positive patients when I was diagnosed, and with a mixed tumor (IDC/ILC/DCIS/LCIS) I don't know what the validity might be. I'd do every bit of the treatment again, knowing what I know.

My insurance did cover most of the test.

Warmly,

Cathy

Oncotype dx for HER2 Positive?

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