Question about Oncotype DX gene expressions

katcar0001

Does anyone know if it is possible or how to get the details on the gene expressions tested by Oncotype DX?

Here is a list of what it tested. I notice none of these details are on my reports, but I am curious because I keep running into articles that discuss these variables. Maybe I have too much of an inquiring mind, lol.

K1-67	ER	Stromelysin 3	GRB7	GSTM1	Beta-actin
STK 15	PR	Cathepsin L2	HER2	CD68	GAPDH
Survivin	Bcl2			BAG1	RPLPO
Cyclin B1	SCUBE2				GUS
MYBL2					TFRC

*** Sorry for the formatting--looks like a table in edit mode.

vlnrph

I did not have that testing (two different lesions plus micromets in sentinel node assured me of chemo) but I think you may be confused about gene expression.

Are the articles you see describing mutations like BRCA 1/2, PALB, ATM, BRIP, CHEK, CDH-1 and all the other alphabet soup of initials associated with human chromosomes? Those are shorthand for some of the codes making up our individual selves and are what we inherit from our parents.

Oncotype is designed to look at the characteristics of your particular tumor and to compare it with others in order to gauge the likelihood of recurrence. Certainly talk to your clinic and, if you have family history that is of concern, hopefully they have a counselor who can explain your options for risk assessment.

lekker

I called genomic health back when I had the test done in August 2012. I was very disappointed that my "21 gene assay" only showed results for ER, PR and Her2. They said that they don't release any other details but never gave a reason why. You can try calling their customer service line at 800-ONCOTYPE (I'm not making that number up). Please post again if you find out anything

katcar0001

Thank you for your responses. Lekker, How disappointing. I'd really like to find out more... I wonder why they keep it so tight to the breast? (no pun intended) I mean, the results are yours. I will call and see what I can find out or maybe have my doctor call. I know it wouldn't make the much difference in my treatment, but I've read some stuff about estrogen-receptor beta and Tamoxifen resistance that has me concerned.

vlnrph, Oncotype does indeed test gene expressions. You can find out more here, although as you said, it was not relevant with your circumstance: https://elcaminogmi.dnadirect.com/grc/oncotype-dx/...

Understanding Gene Expression

Oncotype DX testing measures the activity level of 21 different genes in breast tumors. This is called gene expression testing. These measurements let the laboratory see what factors are driving a cancer. They predict how a cancer is likely to behave in the future.

All cancer is genetic in some way. However, most cancers aren't the kind you inherit. This may seem contradictory at first. The difference lies in understanding when the gene changed the way it works — a change before birth that you inherit from a parent or mistakes that buildup each time your cells copy their genes, to make new cells.

Traditional genetic testing looks at genes you inherit from your parents. It usually targets one gene and looks for specific changes or mutations in the genetic code that you were born with.

On the other hand, gene expression has little to do with heredity or the genetic code. It looks at what the genetic code is making, but not at the code itself. Genes act as instructions to make specific proteins. Gene expression testing measures how active certain genes are. It may help to think of gene expression as a light switch, with a dimmer control. Taking a step back, think of the light bulb itself as the genetic code. This is what is inherited, and doesn't change. However, what that light does in each cell will change. Sometimes the light is turned on to full power. Other times, the light is completely off. Gene expression is the dimmer that controls the light.

When a gene is very active, it has a high expression level. The light is turned fully on. When a gene isn't active, it has very low expression. The dimmer switch toned the light down.

Each tumor and cancer has its own unique gene expression pattern. Each gene contributing to that cancer has its own dimmer switch. Gene expression levels within a tumor may affect how a cancer grows and how it will respond to treatment.

vlnrph

Looks like you have a pretty good understanding of the issues: I was afraid all the new info on multi-panel testing for hereditary cancers was getting mixed up with the science Genomic Health has been a pioneer in. Their website is also educational (especially the professional part) but, having patents on their procedures, I'm not surprised they don't release details of what they probably consider "trade secrets".

besa

http://www.senology.org/Oncotype_DX.pdf

katcar001 - you can get a general idea of what the expression levels are in respect to the genes used in the oncotype dx test. Look at page 37 in the link above. For proliferation genes you probably have KI67 immunohistochemistry (antibody staining) results and know if the cells in your bc are growing quickly or slowly, for HER2 you should also have immunohistochemistry and possibly FISH results, for ER and PR there are immunohistochemistry results.

The "control" genes---- beta-actin, GAPDH, RPLPO, GUS, and TFRC are called "housekeeping genes" and are are not important when it comes to breast cancer. They are used as controls in the assay to normalize the results -- basically correcting for the amount of tissue that is being analyzed.

Not sure what your background is so possibly this is stuff you already know... (if so just ignore the rest :-) The oncotype dx assay uses a laboratory technique called real-time quantitative PCR (RT-qPCR). It looks at the messenger RNA (mRNA) that breast cancer cells are making. Basically to construct a specific protein a cell uses DNA (just a part of it's DNA -- the gene which codes for a specific protein) to build mRNA - this step is called "transcription" (this mRNA also contains a code for a specific protein) and then a cell uses the mRNA to make the protein (this is called "translation"). The oncotype dx test measures the amount of mRNA that is being produced. (They assume the amount of mRNA correlates to the final amount of protein that will be produced. This is generally but not always true). A RT-qPCR test result is a number. The oncotype dx test takes the RT-qPCR number results for individual gene expression and plugs them into a formula that they have figured out -- kind of a model. The final numeral number is the oncotype dx score. Not sure I have done a good job of explaining this but at least a try on my part.

katcar0001

Yes, the Genome Health website has some really good info and graphs. I didn't consider the patent issue.

besa, that paper looks very valuable. I'll give the whole thing a read this evening. Thanks for passing it on.

lekker

I posted the following a while ago on another thread. It explains the role of each gene they test and the multiplier for each group to calculate the score. Since they've published their formula, it doesn't really make sense to me why they won't publish each subscore.

Jul 15, 2014 02:41PM lekker wrote:

I've posted the following on two other threads so far because the issue keeps coming up. The OncotypeDX score is calculated from the expression of 16 different genes and 5 reference genes so a high or low score isn't the result of any one thing in particular, rather the combined scores of ER-related expression (the higher the better) and invasion, HER2-related and proliferation (the lower the better) groups. The post below is combined from the two other threads - one asking about Ki-67 and the other about PR...

Below is my post from the progesterone thread. You can see how genomic health uses Ki-67 as one of the 16 calculations. One thing I think is critical to remember when considering issues like this is that the pathologist (who would be the one to assign a Ki-67 measurement if done as well as ER, PR and HER2) is using a different tumor sample than genomic health would be using. Cancer is a heterogenous disease - it's not impossible to have very different results within the same tumor. Back to the old but original reason for this thread, the OP was concerned because her pathology didn't mention Ki-67 and that made her feel that she wasn't given all of the information she needed to make the chemo/no chemo decision. I too felt shorted because my pathology didn't mention Ki-67 but eventually realized that the oncotype test did measure it - as well as 4 other proliferation genes. Like the OP, I had to be convinced not to do chemo because I wanted to do everything possible to avoid a recurrence. Once I understood that chemo doesn't guarantee a cure and it has its own risks to consider, I agreed that the right plan for me was to forego it.

Here's my post...

the PR score is just one of the factors that goes into calculating the oncotype score. They break down the different genes into groups and multiply each group by a factor they somehow came up with to get the final score. PR is in the "ER related genes" group which is the only group to have a negative multiplier - the higher that group's score, the more it lowers the final result. So if you have low or absent PR expression, it will raise that part of the score. If the scores from the other groups are low, you can still end up with a low score of course - PR is just one piece of the puzzle.

The test was then validated using 675 node negative ER positive tamoxifen treated cases from NSABP B-14. In this analysis given classes of genes were given previously determined weighting factors and prognostic scores were calculated. The weightings would seem to make sense with proliferation, Her2 related, and invasion group genes increasing the score and ER related genes decreasing the score. The score was a continuous variable, but for the convenience of the presentation the patients were divided into 3 groups using cut points of 18 and 31.

Hopeful82014

lekker - thanks so much! I'd not seen that elsewhere and it's most interesting. Do you know if it used the same information in the same way when scoring node-positive disease?

lekker

Hopeful - I believe it's the same test that's now being used with a limited number of positive nodes

Meow13

It used to be the size and extent of the spread were the only factors in the prognosis now with actually comparing and testing gene expression is what determines prognosis

katcar0001

I am learning a lot! Besa, I did not know about the control genes

Lekker, the posts you forwarded had some really good info--esp. the invasion scoring bit. I had not seen these when I searched.

Thank you, peeps, for all this material.

vlnrph

Some of you may be interested in a magazine called Genome that I found at my doctor's office last month. It's a quarterly that's going into a second year of publication and i just began a free subscription. (Most recent edition includes several pages of ads but that's what covers the cost!)

Their tag line is "Your Health is Personal". Our Howard Jacob here in Wisconsin is on the board of advisors. You can find back issues at genomemag.com, they also twitter & have a facebook page.

Hopeful82014

Thanks for the heads up, VLN.