Need help interpret Oncotype DX result

jenrio

I got my oncotype DX result:

My her2 score is 7.6, less than 10 cutoff for positive.   So I am Her2-.

But I don't know what the 7.6 means.   Does it mean I will not respond to Herceptin at all?   Or am I just going to respond less than Her2+ people?   If so how much less?

Also, is there a way I can get the detailed report from Oncotype DX?  I thought they are supposed to test for 21 genes, but the final report is just ER,PR, HER2 plus a total score.   I was hoping for a bit more information...

Thank you all!

Halah

Her2 is determined by the pathology. The oncotype dx score for me is 16 so I didn't need chemo. Perhaps your score is 7.6? I would contact your doctor if I were you. Good luck! 

Sherryc

When I asked my MO for the results he only made the copy of the sheet with the scores on them.  I later got the full copy from my RO's office when I realized there were more pages that I did not receive. I was in radiation by the the time I realized it and it was just easier to get it there.

hlya

jenrio: Her2 score is NOT Oncotype score, they are totally different.

Is 7.6 for HER2 or Oncotype test?

Also, if your HER2 negative, you do not need Herceptin at all.  It doesn't matter whether you respond to it or not, you just do not need it. 

jenrio

Her2<7.6

OncoType is a bit scammy.  They advertise 21 gene panel, but they will only give the patient details on three genes:  ER,PR,HER2.    I have Her2 negative, and ER+PR+  but recurrence score is borderline high.   So the other 18 genes must be the culprit.   Only I have no idea what they are...  Sigh

hlya

The method they tested HER2 is the same as FISH (what was used in your pathology report)

To determine whether you are HER2 positive or negative, is based on how much % of your cancer cells are "over-expressed",  if you are below 7.6, it means only 5% or 10% (I do not remember the actual number) of your cells are over expressed, which should be shown as HER2- in your pathology report.   Some people have a little bit higher % than you (eg. from 7.6 - 10.7)  which is shown as HER2 1+ but still considered as HER2 negative.  2+ means equivelant which needs to be re-tested, 3+ means "over expressed".   If you are not over expressed you do not need Herceptin at all.

ER, PR and HER2 are NOT 3 of the 21 genes,  they are not genes.  They are just some biological features of your tumor。

The way they tested the genes are not the same as what was done in pathology - in pathology report they do not test those genes.  If your score is high, it means your cancer cells should respond to chemo better than tamoxifen (or what-ever anti-hormone treaments)

BTW, what are your ER and PR scores? 

ScienceGirl

http://www.nejm.org/doi/pdf/10.1056/NEJMoa041588

Here is the link for the original paper published in 2004 discribing the Oncotype score.  The paper states the 21 genes, which includes 5 refence genes.  ER (estrogen receptor), PR (progestrone receptor) and HER2 are proteins - the genes that encoded these proteins are part of the 21 gene set.  

I think the reason that they don't give out all the gene results for the score is that it would be meaningless.  Each of genes is weighted differently in the algorithm and some genes push the recurrence score higher and some push it lower.  See the paper

Proliferation Ki67 STK15 Survivin CCNB1 (cyclin B1) MYBL2 HER2 GRB7 HER2 Estrogen ER PGR BCL2 SCUBE2 Reference ACTB (b-actin) GAPDH RPLPO GUS TFRC Invasion MMP11 (stromolysin 3) CTSL2 (cathepsin L2)

Figure 1. Panel of 21 Genes and the Recurrence-Score Algorithm. The recurrence score on a scale from 0 to 100 is derived from the reference- normalized expression measurements in four steps. First, expression for each gene is normalized relative to the expression of the five reference genes (ACTB [the gene encoding b-actin], GAPDH, GUS, RPLPO, and TFRC). Reference-nor- malized expression measurements range from 0 to 15, with a 1-unit increase reflecting approximately a doubling of RNA. Genes are grouped on the basis of function, correlated expression, or both. Second, the GRB7, ER, proliferation, and invasion group scores are calculated from individual gene-expression measurements, as follows: GRB7 group score = 0.9 ¬ GRB7+0.1¬HER2 (if the result is less than 8, then the GRB7 group score is considered 8); ER group score = (0.8¬ER+1.2¬PGR+BCL2+SCUBE2)÷4; proliferation group score =(Survivin+KI67+MYBL2+CCNB1 [the gene encoding cyclin B1]+STK15)÷5 (if the result is less than 6.5, then the proliferation group score is considered 6.5); and invasion group score=(CTSL2 [the gene encoding cathepsin L2] +MMP11 [the gene encoding stromolysin 3])÷2. The unscaled recurrence score (RSU) is calculated with the use of coefficients that are predefined on the basis of regression analysis of gene expression and recurrence in the three training studies24-26: RSU=+0.47¬GRB7 group score¡0.34¬ER group score +1.04¬proliferation group score+0.10¬invasion group score+0.05¬CD68 ¡0.08¬GSTM1¡0.07¬BAG1. A plus sign indicates that increased expression is associated with an increased risk of recurrence, and a minus sign indicates that increased expression is associated with a decreased risk of recurrence. Fourth, the recurrence score (RS) is rescaled from the unscaled recurrence score, as follows: RS=0 if RSU<0; RS=20¬(RSU¡6.7) if 0≤RSU≤100; and RS=100 if RSU>100.

mawhinney

For a better understanding of the Oncotype Dx test check out the topics at the very top of this screen. Click on Symtoms and Diagnostics 7 then Screening & Testing.

otter

Here's a link to what Genomic Health says about the technology behind their Oncotype DX test:

http://www.oncotypedx.com/en-US/Breast/HealthcareProfessional/Underlying.aspx

On that page, they list the "21 genes" they assay in their test.  But, they aren't measuring either the proteins (ER, PR, HER2 etc.) or the genes.  They're measuring the amount of messenger RNA (mRNA) the tumor cells are transcribing from each of the genes on that list.  In other words, the Oncotype DX test detects whether, and how enthusiastically, the tumor cells are using ("expressing") those genes.

Of the 21 genes in the Oncotype DX test, 16 are relevant to cell growth, and therefore to cancer.  Some of those 16 are known to be associated with aggressive growth of cells and worse prognosis (the genes in the "Invasion" and "Proliferation" groups, for instance).  The test results for expression of those genes are assigned positive weighting in the formula for the "Recurrence Score."  Other genes are known to be associated with slower growth and better prognosis (the genes in the "ER" group are examples of these).  Those test results are assigned negative weighting in the formula.

There are 5 additional genes, besides the 16 growth-related genes, whose expression is measured so the test results can be normalized.  Those genes are in the "Reference" group.  Normalization is a laboratory strategy necessary to allow the results to be compared to reference values and to results of tests done on other samples or other days.

I know it's frustrating to think that Genomic Health might be collecting other results that could be useful to us, but they're refusing to release those results.  That's not accurate, though, and it's not fair to the company to characterize what they do as "scammy".  Even if Genomic Health has numbers for expression of the other genes (the ones they test in addition to ER, PR, and HER2), it would not be helpful to give those individual numbers to us or to our doctors because they're meaningless by themselves.  Even the values for ER, PR, and HER2 don't make much sense all by themselves (what does "7.6" mean?).

The values for expression of the individual genes would have to be analyzed statistically to see if they correlated with something clinically relevant.  That takes big clinical trials with lots of tumor samples and long-term outcomes (Who survived?  Who had a recurrence?). 

Genomic Health did those clinical studies to validate the assay (the significance of the "Recurrence Scores"), and they did those studies to determine positive/negative cutoff levels for ER, PR, and HER2.  But they don't have results of studies that would explain whether a score of "2.3" or "11.6" or "17.8" for, say, BAG1 or Survivin gene expression, means a greater or lesser likelihood of metastasis. I don't know if they're even doing those studies on the other genes.  Genomic Health adds information to the reports they send as they gather the data and complete the studies.  (There were no individual results for HER2 when I received my Oncotype DX report early in 2008.)

It seems like we're always having to make decisions without enough information, doesn't it? <sigh>

otter

treeskier

Jenrio, what is your oncotype DX recurrence score? You said it was borderline high.

PLJ

Well said, Otter.

jenrio

Thanks Otter/ScienceGirl for some very good information!   

My ER is 7.4, just above cutoff at 6.5

My PR is 6.9 just above cutoff at 5.5

My Her2 < 7.6

RS = 29

 Does that make me weakly ER+,PR+ and Her2 negative?