The Genetic Test Results

 I originally wrote this post in January 2017 but just realized that I never published this until now. I had forgotten it was in the drafts.... but this is relevant to my next post. 

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 January 2017

This post is definitely overdue.  In part, I was trying to wrap my head around it.  The initial appointment with the genetic counselor discussing the results was overwhelming in itself.  I needed the time to process and understand what my genetic test results meant.  I spoke with a brilliant guy who loves genetics.  I am grateful to my colleagues who helped connect us.  He helped me understand genetics somewhat better.  I think I need years of study before I fully understand the whole genetics thing.  I am grateful to him for helping edit this post.

My take-home message was that while it is good news that I tested negative for all 25 cancer genes, but it's still a MAYBE.  I MAY still have a risk because I have a variance of one gene.  Can you see why this can easily mess with one's head?  It's like, "You're okay... but... wait a minute... maybe...."

While I was in the process of understanding all the information I was given, Dr. Jewell's initial recommendations that I have my breasts and ovaries removed utterly freaked me out.  I put the genetics test results aside for the time being.  I think I avoided dealing with it because I did not want to face the possibility I may have to go under the knife again.  Three surgeries in one year is simply too much.  I do not want any scalpel near me for a long time.

As I stated in an earlier post, I was tested for the following genes:

BRCA 1/BRCA 2
MLH1
MSH2
MSH6
PMS2
EPCAM
APC
MUTYH Biallelic
MUTYH Monoallelic
CDKN2A (p16INK4a)
CDKN2A (p14ARF)
CDK4
TP53
PTEN
STK11
CDH1
BMPR1A
SMAD4
PALB2
CHEK2
ATM
NBN
BARD1
BRIP1
RAD51C
RAD51D

The bold-faced ones are tied to uterine/ endometrial cancer.  I tested negative for those.  Hence, I will never know why I had endometrial cancer.  It could be a combination of environmental and physical factors.  I tested negative for all cancer genes.  However, I have an uncertain variant of the gene BRIP1 (italicized).  Specifically, my genetic test results state the following: "c.2220G > T (p. GIn740His).  At this point, we do not know if this variance poses a cancer risk.  There's not enough data.  If and when there are additional data, they will be able to make an informed conclusion whether that variance is a concern or not.

The BRIP1 gene is tied to ovarian and female breast cancer.  The risk for ovarian cancer with this gene is at 8.3% or higher while the risk for the general population is 1.1%.  The risk for breast cancer is at 10-20% or higher and 10.2% for the general population.

During this process, I also insisted that Dr. Jewell follow through with her promise to get a consult with MSKCC's Genetics Team.  Genetics team said I had to travel back to New York City for a formal consultation.  I was not willing to do that because I already had the genetics counseling appointments locally.  I was frank with Dr. Jewell about my feelings.  I told her that I wanted to discuss my genetics test results with her and her quick response was that maybe I should play it on the safe side and get my breasts and ovaries removed.   I further explained that recommendations contradicted with my genetics counselor's recommendations.  And I was not willing to get a formal consultation with the Genetics Team at MSKCC to find out if Dr. Jewell had sound recommendations.  Instead of talking with Dr. Jewell via her nursing staff, Dr. Jewell finally replied to me directly after a few weeks:

"I did reach out to the genetics team to clarify what the current recommendations are for variants of undetermined significance since this is an evolving area of research and I am learning about these new mutations.  Unfortunately, the genetic counselors at MSK do not make recommendations about patients without a formal consultation. However, I did find out that in general surgery is not currently recommended for these variants of uncertain clinical relevance. That said, family and personal history are components of the conversation with the genetic counselors to determine final treatment plans. I really am unable to offer more guidance. It seems that your local genetics team is up-to-date and a good resource. The genetics team here continues to be available if you would like to pursue their more personalized opinion."

That reply calmed me a bit.  "Surgery is not currently recommended for those variants..."  Then I decided to put it all aside for a while.  The whole process caused me some emotional turmoil.

It was much to my relief to learn that Dr. Angel share similar recommendations as the genetic counselor.  I do not have to do anything right now.  I have to be monitored continually to make sure nothing else comes up.  That means routine CA-125 tests which looks for tumor markers for ovarian cancer plus routine mammograms.  I have had two CA-125 tests done since August and am in the clear.  I had a mammogram last September and everything looks good.  I will be having an ultrasound of my ovaries in February because I mentioned that I was feeling some pain in the ovaries from time to time.  Before the cancer, I had functional ovarian cysts on a monthly basis.  I had become accustomed to this monthly pain.  After the hysterectomy, I only experience it once every few months.  I mentioned this to Dr. Angel at the November appointment.  She raised her eyebrows and looked at her nurse practitioner who was also in the room.  She said it would be worthwhile to take a look to see how my ovaries are doing.

Women with BRIP1 are recommended to consider surveillance, oophorectomy (removal of ovaries), or chemoprevention to manage the risk of ovarian cancer.  Since the risk for breast cancer is almost similar to the general population, regular or frequent screenings are recommended.

It's not confirmed that I tested positive for BRIP1.  I just have an uncertain variance.  What does this mean for me?  I just have to go on with my life and participate in the surveillance plan for my ovaries and breasts on top of the ongoing surveillance plan for endometrial cancer.  The genetics lab will notify my genetic counselor if there has been a change in the data regarding the gene variance.  My genetic counselor explained to me that I must constantly communicate with the office if my contact information changes so they can find me if and when new information emerges.  It could be next year... it could be in five years... it could be 20 years... it could be never.  I am not going to sit around and wait.  I'm going to live my life and deal with it if and when I get the phone call from the genetics counselor.  We don't know.  Genetics research continue to expand exponentially.

The genetics genius that I spoke with explained that I do have the BRIP1 mutation but I have a variance of that mutation.  "c.2220G > T (p. GIn740His).  The letter T is the variance as opposed to the letter G.  (Jeff is this correct?) It is unknown at this time if that variance would mean I have an increased cancer risk.  It could be a good variant but it could also be a bad variant.  He said that BRIP1 gene mutations are related to the well-known BRCA1/BRCA2.  It is important to emphasize that having a gene mutation does not mean one would get cancer.  It just means there is a risk.  There are number of factors that cause the cancer to emerge.  He said that the variance is one thing but I may have other genetics that came into play that caused the endometrial cancer.  I asked how the mutation and variance happen.  He said it was a result of years and years of evolution and environmental factors that caused our DNA to mutate.  It is through our biological survival mechanisms that create variances.  Sometime variances mean more bad news but sometime they mean nothing.  There's no clear answer.   Essentially, we are still swimming in the land of unknown with this whole genetics business.