Foundation One came back, ATM (Alteration R250, loss exons 19-20)

[cfrees1]

Just found I that I have the ATM mutation. While I always believe that some knowledge is better than no knowledge, this news is not the best for me. At least it explains why ADT doesn't seem to last for me for very long. Right now, Apalutamide/Lupron combo is keeping my PSA down around 0.2 and it's been steady for a few months. I'll be looking for news on any new treatment options or clinical trials for ATM defects. Please keep your eyes out for me as well. Any others with this defect who have had some success with treatments? What has been your path? Thanks.

[Tall_Allen]

That also means your tumors are more susceptible to radiotherapy and chemotherapy. You should rule out germline ATM defects, however.

[cfrees1 in reply to Tall_Allen]

By "suscpetible", you mean they will respond to those treatments well? As I read further in the report, Microsatellite status was MS-Stable, TMB-Low, and VHL-P815. I don't think any of those things are good...

[Tall_Allen in reply to cfrees1]

Yes- they make the tumor more vulnerable to those treatments. MS-Stable and TMB-Low is normal - it just means Keytruda probably won't help you, just as it doesn't help most men with PCa.

[cfrees1 in reply to Tall_Allen]

I understand the online definition of germline (inherited via the sperm or zygote) but I don't really understand how that relates to my situation or treatment plan. Can you help me understand that better please? Certainly if they are germline, I should let me family know to keep a close eye on their own health, but beyond that, what is the impact? What should I be watching for?

[Tall_Allen in reply to cfrees1]

FoundationOne tests the tumor for mutations. Other tests (like Color Genome Dx - below) tests whether that mutation is carried in all of your cells. That is unlikely, but for $200, you can rule that out. If the ATM defect is germline also, radiation and chemo will be too toxic to all your healthy cells.

pcnrv.blogspot.com/2018/02/...

[cfrees1 in reply to Tall_Allen]

Interesting, so if I had adjuvant radiation (and I did) and didn't suffer side effects (which I didn't), then the chances are that this mutation is NOT germline? is that a correct assumption?

[Tall_Allen in reply to cfrees1]

That is certainly correct. You would know it (painfully) if you had a germline ATM defect and you had radiation.

[cfrees1 in reply to Tall_Allen]

Thanks for you prompt responses. Now we wait to see what's next I guess.

[sammamish in reply to cfrees1]

I have an interest in this topic as I am ATM germ positive and have been studying it for a while now. The below meta study is probably the best info on this topic to date as far as I know.

ncbi.nlm.nih.gov/pmc/articl...

Basically, if you are a heterozygous carrier for ATM your odds are 1.5 X for early adverse reaction and 1.2X for late term adverse affects due to radiation. So for your average joe what does that mean? I guess if the average incidence of short term adverse affects for a standard course of IMRT is say 4%, then you would expect to see 6% in an ATM cohort population. This doesn't sound so bad until you read some of the anecdotal reports in the literature of folk having horrific radiation reactions. There is a fair amount of one off clinical reports in places like JAMA especially with breast cancer and BRAC and notably contralateral breast cancer(cancer induced by radiation of the other breast).

So this begs the question what to do if germ line ATM positive with PCa? Roll the dice on radiation and hope not to be one of the 6%? Maybe 6% percent isn't a bad number? Then again no clear cut studies on secondary cancer with this condition. I would assume some impact. Also, one might expect other DNA damaging therapies like Parp inibitors or Carboplatin would also be detrimental to healthy cells.

Then there is the thought of attempting to protect healthy says by say fasting prior to treatment ( ncbi.nlm.nih.gov/pmc/articl... ), but wouldn't this also protect PCa cells from the radiation or Carbo since the vulnerability is the same in for the healthy tissue and cancer tissue?

Maybe something more targeted like Luteium is the only way around issue?

This question has been quite vexing for me.

[Cmdrdata]

This a general question pertaining to DNA testing that perhaps someone following this tread, especially TA knows. Is there a list of PCa related mutations vs what drugs/radiation etc. that are effective or non-effective treatment wise? For example cfrees1 has ATM thus localized radiation to the tumor is most likely effective and have little SEs. What about ARv7, BRCA1/BRCA2, HER, PSMA expression etc. etc.?