Question about Oncotype DX gene expressions

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.

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.

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.

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

Thanks for the heads up, VLN.