ATM gene..impact and typical surveillance procedures

Janeway69

This actually started with a genetic screening of my mom's tumor. She has stage four Pancreatic adenocarcinoma, not BC.
However the results came back positive for a variant of the ATM gene. I do not know which yet. My mom is bringing the report this weekend.
I called the genetic counselor who saw us at Memorial Sloan Kettering (mom gets treated there), who said she did not know what variant mom had but she felt it didn't matter, because she said all variants give no more than a 30% lifetime risk of BC and persons with a copy of the gene, get additional screenings like breast MRIs. She said ATM genes are "low penetrance" genes. She also said a Dr. Mark Robson from MSKCC wrote something in 2017 about it. I keep looking around on the MSKCC listings of his published papers but so far, I don't see this journal article.

Anyway, what set this off is my regular GYN who flipped on me, and said this was much more serious than MSKCC was making it out to be. SHe also said some variants, or at least one anyway, DOES have a 70% lifetime risk.

The counselor said "I don't know your GYN but I have no idea where she is getting this."

You can imagine how confusing this is to me. My GYN was almost talking about radical mastectomy as a prophylactic option IF I have inherited an ATM gene from my mother.
I have not had any testing done on myself yet.

Does anyone know anything further about this particular gene? Thanks.

ReadyAbout

I think what matters is the specific nature of the variance. For example, I have an ATM VUS mutation, meaning "variable of unknown significance", meaning they haven't done enough research to reclassify it. The geneticist told me that ATM VUS is an alteration, not a mutation. An alteration is like putting 2 TB of cinnamon instead of 2 tsp in an apple pie recipe - it will taste different but it will still be apple pie. A mutation is like putting 2 tsp of arsenic instead of 2 tsp cinnamon - you've got a real problem with the pie. My alteration should have no impact on the normal treatment protocol and it should withstand radiation just fine. Of course, I have to wonder if they've done any longitudinal studies on this yet - have they tracked women with ATM VUS over 10-20 years to see how they did post-radiation? In any case, I couldn't do radiation for other reasons so I'll never know. I hope this meandering explanation helps a bit. A standard ATM gene mutation does increase risk for both BC and pancreatic cancer.

Janeway69

Thanks ReadyAbout. It does explain some things. I read in some places that ionizing radiation can cause BC, or is thought to, in people with ATM mutations. How do doctors decide whether or not to give radiation or even mammograms with X rays to women with this gene mutation?

Janeway69

Hi ReadyAbout. So, I don't mean to be scary but I got a hold of my mom's copy of reporting from the genetic counselor. It's a summary with a fair amount of info for the layman. It doesn't answer ALL my questions but my variant is c.5290delC. About to head to work so not writing the details here. Googling results in some studies but one or two mention "considered pathogenic." I don't think mine is a VUS.
However, somewhere in the description it mentions "this alternation is.." so it refers to it as an alteration but also a mutation, and ultimately still with the higher risk.

So, I'm not sure if "alteration" is really anything different. I mean, being mutated is to be altered when you think about it. I'm going to ask the counselor if professionals actually use those two labels to mean separate issues. Maybe the word is being used differently in this paper vs what you were told. It specifically says "This alteration is predicted to lead to a truncated or absent protein, and truncating variants in ATM are known to be pathogenic."

It also says this is a "moderate risk" breast cancer gene, and persons with it carry a lifetime risk of BC that is 2-3 times that of the general population.

I was told by my counselor that it's a "low penetrance" gene, but stuff I read online says people with tumors caused by this have a poorer prognosis. I'm just trying to get more feedback.
Someone PM'd me and asked, if this were such a scary gene, why aren't people talking about it more like BRCA genes etc. I don't know but I do read in my report that my variant at least has been identified in 0.0015% of non-Finnish Europeans. I don't know what that says about the total number of persons out there walking around with ATM mutations, but maybe it's just not as common?

Were your doctors able to say if your BC was directly related to your alteration? You said you could not get mammograms for other reasons.

Janeway69

One other word. I just want to apologize if I am jumping the gun and being scarier than I have a right to be.

Someone showed me a good article that helps give another perspective.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513673/#!po=27.1429

Also, the report my mom got from the genetics counselor said that the risk of Pancreatic Cancer is increased by 3%-5% by her variant.
Not terribly huge numbers.

I think my super-cautious GYN just shook my nerves. The fact that she knocked the genetics folks at Memorial Sloan kettering saying "I bet they were all Laizzez faire about it" didn't help.

I wish you the best in your treatment and recovery. Is there an estimation of the road ahead?