Question about P16 Gene Expression

Deirdre1

Hi all (Beesie you might be able to address this).  Is anyone aware if the test to check DCIS for an over expression of the P16 gene is available yet?  Also do you know if the testing has to be done on the "fresh" tissue directly from the biopsy or surgery or if the test can be performed on a slide from a prior dx?  I have sent out an e-mail to Dr. Gauther (main researcher on this) but haven't heard anything back yet (I'm sure she is incredibly busy) so I'm hoping someone here might have some helpful information on the subject. 

This info is relatively new and apparently it goes directly to the question we all have asked on this board or in our heads, "does my DCIS have the potential of going invasive" or "how can I tell if my DCIS will become invasive".  I'd appreciate any input on the matter!!!  Thanks in advance!

Deirdre1

Bump

IronJawedBCAngel

The results of this study were just recently released, and my understanding is that they do not expect that patient care will change immediately, which indicates to me that they will not start checking for these markers.  Hopefully Dr. Gauther will shed some light on it for you.  I imagine if you are treated at a large cancer center that participates in a lot of research, your odds will be higher of them testing for the markers.

P16 is just one of the markers that they studied, Cox 2 and Ki67 were included in the study.  They also focused on women who were diagnosed because of a palpable lump, not a mammogram. MRI's were not included because the control group were from a period of time before breast MRI's were being done. The increase in risk for being positive for all three markers and being diagnosed with a palpable lump put your risk factor at 20% over 8 years.  Those who are negative for all three markers and had their DCIS diagnosed through a mammogram have a risk of 4% over the same period of time.  I have not read the complete study and do not know what your risk is if you are positive for just one marker. (ie P 16)  I just find the research encouraging in that these markers will help develop more targeted treatment plans for DCIS patients in the future.

Beesie

Deirdre, sorry for not responding sooner.  I wanted to do a bit of research on the topic. 

As Jenn said, p16 is one of 3 biomarkers that were found to be correlated to recurrence risk in this latest research (and in quite a few previous studies, as I've now found); Cox-2 and Ki67 are the other two.  In the most recent study, seven biomarkers (underlined below) were tested and it was the presence of these three within the DCIS pathology sample that was found to be linked to a higher risk of a subsequent invasive cancer.

"The study also found that different combinations of biomarkers measured on the initial DCIS tissue were associated with varying levels of risk of invasive cancer or DCIS. These biomarkers include estrogen receptor, progesterone receptor, Ki67 antigen, p53, p16, epidermal growth factor receptor-2, and cyclooxygenase-2. Women who express high levels of p16, cyclooxygenase-2 and Ki67 were more likely to develop invasive cancer after their initial DCIS diagnosis."  http://www.sciencedaily.com/releases/2010/04/100428173335.htm

Searching for info on breast cancer pathology reports, it's apparent the Ki67 is commonly tested, but currently only for those with invasive cancer.  COX-2 and p16 don't appear to be tested for regularly (I couldn't find any reports on "how to interpret/read a breast cancer pathology report" that even mention COX-2 or p16).  I don't know how difficult it would be - or how costly - to get these tests done.

What I did find out is that testing can be done after the fact.  This is in fact how this recent research was done.  The DCIS pathology samples that were reviewed in this study were from 1983 to 1994 and the testing was done at a much later date:

"We collected clinicalcharacteristics and information on subsequent tumors, definedas invasive breast cancer or DCIS diagnosed in the ipsilateralbreast containing the initial DCIS lesion or at a regional ordistant site greater than 6 months after initial treatment ofDCIS (N = 324). We also conducted standardized pathology reviewsand immunohistochemical staining for the estrogen receptor (ER),progesterone receptor, Ki67 antigen, p53, p16, epidermal growthfactor receptor-2 (ERBB2, HER2/neu oncoprotein), and cyclooxygenase-2(COX-2) on the initial paraffin-embedded DCIS tissue."  http://jnci.oxfordjournals.org/cgi/content/abstract/102/9/627 

So that at least answers one of your questions!

By the way, I find it interesting that HER2 was one of the biomarkers that was included in this test yet the results don't mention that there was any correlation between HER2+++ DCIS and invasiveness.  This is always a hot topic of debate around here.  To-date, there have only been a bunch of small studies on this and the results on HER2 status and DCIS have been mixed, with some studies showing a relationship and others not.  The most recent study, released last year, suggested that there was a correlation between HER2+++ status of DCIS and the risk of invasiveness.  This study now seems to be saying that this is not the case.  So this may be one more study that goes into the "HER2 status has no impact" column. 

Deirdre1

Thanks Beesie you most certainly did answer the question about if the tests can be run retrospectively!  Thanks!  I was only able to find a summary of the report so thanks for this link!  It is so interesting how many things are changing all the time.. my bs told me that she was always concerned when a mamo or MRI showed DCIS but there was no lump and this report shows the opposite..  Now I do understand that this is new research and so there will be more to follow.. but I might call my genetic counselor and ask about the COX-2 & P16.

Thanks Jenn also for helping with the search!

We had another loss in the family this weekend - a different cancer (not breast cancer) and it's impact was incredible - such a loss at 16 years of age.. almost incomprehensible!  In our family, at least, cancer seems to be just waiting around the corner!  I think I am in shock a bit so this one is short.. but thank you both for your time and attention!!!  Best, Deirdre

Deirdre1

Just a quick follow-up.  Today I received a response from Dr. Gauther and it was brief and it stated the research is too new and the tests are not available yet for patients..  No wonder we couldn't find too much info on it!!!  Take Care, Deirdre