Sorry, new to site and didn't post question right. my dad was diag dec 6,2012. He has nsclc adeno stage IV 1.7 cm nodule in ULL with one bone met at 5th rib. His mutation report came back and onc called to say he tested postitive for 2 mutations and that it was rare for that to occur and tx woud be harder. No details on type of mutation. He wants to speak in person. Any suggetions or advice would be much appreciated.
I'm very sorry to hear of your father's diagnosis.
It could be that he has an activating EGFR mutation and also one associated with resistance, or that he has an activating EGFR mutation and also a KRAS mutation, which tends to be associated with a less robust response to an EGFR inhibitor. I don't think it makes a lot of sense to speculate until you learn what the mutation testing actually showed.
Here are links to a few posts where you can learn more about the general concept of mutation testing in lung cancer:
There was actually a publication just out in "Journal of Thoracic Oncology" that reported on 11 patients with "compound mutations", a combination of a known activating mutation and another mutation less well characterized, perhaps one associated with resistance. Most of the people who had compound mutations and who received an EGFR inhibitor experienced a pretty good response to this treatment, though the numbers are small, and "results will vary" from case to case.
Dr West,
Thank you so much for your response. I called my dad's oncologist today, hard to wait till Friday. He was able to speak for a minute. He said it is complicated, but basically he tested positive for EGFR and positive for two variances of that EGFR, one that is mutated and one that he was BORN with. He has not not had any treatment at all, diag. was on Dec 6, 2012 and we have been waiting complete testing that required two different biopies. He said one variance can be treated with a target pill while the other most likely could not. He said he had only heard of this occurence 4-5 times in the world. (poss. over exaggerated) he said my dad could have passed on the variance to me and my sister as it is genetic dna. And I assume so on and so fouth to my kids. Dont know, but scared for my dad and my family. I assume he was refering to the T790M mutation but didnt say, as I guess he thought I wouldnt know differnce anyway, Any insight you may have to pass on is appreciated as I am going with dad to see onc on Friday. Thank you in advance, and I'm going to look at the link you sent right away..
Callie
PS... in addition, the pathology was done via Snapshot. not sure what that means but said it was not FDA approved but is what Vanderbilt Univ. uses at their clinic.
I think you'll need to get all of the details you can from the oncologist. This is definitely a very unusual situation, so I don't think it'll be possible for me or any of the other faculty to offer much additional insight here.
I agree with Dr West that you need as much detail as possible. However, I thought you might be interested in this thread, started by someone who inherited the T790M mutation: http://cancergrace.org/topic/inherited-t790m-mutation
As you'll see, this lady arranged for her adult children to have genetic screening and counselling. And her thread suggests that Vanderbilt already have experience of this phenomenon, which may reassure your father. It is good to be treated at an institution where they have seen something unusual like this before.
sNaPshot is a test for a range of mutations developed at Harvard, as described here: http://www.guardian.co.uk/science/2011/nov/09/multiple-gene-test-treatm…
best to your dad.
Certain spring: thank you for your reply and the reference to the post about t790m. I did read it and made a reply, hopefully she still checks the site. Trying to locate more information on this, again thank you
Thank you for the posts. I did view them. Dad was positive for the t790m germline. We see the genetics doctor this Tuesday. She will tell us more about it, it's at Vanderbilt and they are partnered up with Dana Farber. I'm glad to help with the research from our end but it still stinks that its my family with this genetic DNA that appears to be harmful. Concerned about my children. This cancer has already taken many people I love. Thanks again for the posts.
Callie.
Yes, I understand, but although it is a bad thing today to inherit it, it might be better news for future generations who unfortunately do have an inherited T790M and know it.
If a person knew at a young age that they had a risk factor for a bad version of lung cancer, they could be hyper-vigilant throughout their life to avoid all exposures to even minor risk factors like 2nd hand tobacco smoke, dust, chemical fumes, pesticide fumes, etc. I assume that not everyone with inherited T790M develops lung cancer.
And since T790M is the most common version of resistance to 1st generation EGFR mutation inhibitor drugs, another 20 years of research might lead to really great ways to control that for years, if caught early enough. Maybe there will even be something targeted very narrowly at just T790M and nothing else (i.e., no significant side effects) that can be used by people with an inherited T790M?
In that sense, your family's participation in that research benefits your descendants and everyone else who is in the same boat. If it the research does achieve what I hope it will in a couple of decades, your descendants should consider you their hero.
My mother (soon), her father, and his father died of lung cancer.
What is the first step I should take from a genetic standpoint to help contribute here. All I know is that she is EFGR- . In fact I'm not even sure, since I haven't seen the report, only gotten a verbal from my mom's onco.
(sorry I posted this in the wrong thread, I had too many open).
You can speak with a genetic counselor about the probability that there is a genetic component, though there isn't commonly a significant genetic component compared with the environmental ones like tobacco and other carcinogens. We're more concerned about familial connections in people whose family members died at a relatively young age of the same cancer.
Reply # - January 21, 2013, 05:28 PM
Reply To: Tested positive for 2 mutations
Sorry, new to site and didn't post question right. my dad was diag dec 6,2012. He has nsclc adeno stage IV 1.7 cm nodule in ULL with one bone met at 5th rib. His mutation report came back and onc called to say he tested postitive for 2 mutations and that it was rare for that to occur and tx woud be harder. No details on type of mutation. He wants to speak in person. Any suggetions or advice would be much appreciated.
Reply # - January 21, 2013, 05:53 PM
Reply To: Tested positive for 2 mutations
I'm very sorry to hear of your father's diagnosis.
It could be that he has an activating EGFR mutation and also one associated with resistance, or that he has an activating EGFR mutation and also a KRAS mutation, which tends to be associated with a less robust response to an EGFR inhibitor. I don't think it makes a lot of sense to speculate until you learn what the mutation testing actually showed.
Here are links to a few posts where you can learn more about the general concept of mutation testing in lung cancer:
http://cancergrace.org/lung/2010/10/10/overview-of-molecular-markers-in…
http://cancergrace.org/lung/2010/10/31/integration-of-molecular-markers…
Good luck.
-Dr. West
Reply # - January 22, 2013, 10:52 AM
Reply To: Tested positive for 2 mutations
calliem3, don't despair yet - we've seen people on GRACE do well even though their mutation profile supposedly work against them.
Reply # - January 22, 2013, 04:18 PM
Reply To: Tested positive for 2 mutations
There was actually a publication just out in "Journal of Thoracic Oncology" that reported on 11 patients with "compound mutations", a combination of a known activating mutation and another mutation less well characterized, perhaps one associated with resistance. Most of the people who had compound mutations and who received an EGFR inhibitor experienced a pretty good response to this treatment, though the numbers are small, and "results will vary" from case to case.
-Dr. West
Reply # - January 22, 2013, 05:15 PM
Reply To: Tested positive for 2 mutations
Dr West,
Thank you so much for your response. I called my dad's oncologist today, hard to wait till Friday. He was able to speak for a minute. He said it is complicated, but basically he tested positive for EGFR and positive for two variances of that EGFR, one that is mutated and one that he was BORN with. He has not not had any treatment at all, diag. was on Dec 6, 2012 and we have been waiting complete testing that required two different biopies. He said one variance can be treated with a target pill while the other most likely could not. He said he had only heard of this occurence 4-5 times in the world. (poss. over exaggerated) he said my dad could have passed on the variance to me and my sister as it is genetic dna. And I assume so on and so fouth to my kids. Dont know, but scared for my dad and my family. I assume he was refering to the T790M mutation but didnt say, as I guess he thought I wouldnt know differnce anyway, Any insight you may have to pass on is appreciated as I am going with dad to see onc on Friday. Thank you in advance, and I'm going to look at the link you sent right away..
Callie
Reply # - January 22, 2013, 05:17 PM
Reply To: Tested positive for 2 mutations
PS... in addition, the pathology was done via Snapshot. not sure what that means but said it was not FDA approved but is what Vanderbilt Univ. uses at their clinic.
Reply # - January 22, 2013, 10:29 PM
Reply To: Tested positive for 2 mutations
I think you'll need to get all of the details you can from the oncologist. This is definitely a very unusual situation, so I don't think it'll be possible for me or any of the other faculty to offer much additional insight here.
Good luck.
-Dr. West
Reply # - January 23, 2013, 01:34 AM
Reply To: Tested positive for 2 mutations
I agree with Dr West that you need as much detail as possible. However, I thought you might be interested in this thread, started by someone who inherited the T790M mutation:
http://cancergrace.org/topic/inherited-t790m-mutation
As you'll see, this lady arranged for her adult children to have genetic screening and counselling. And her thread suggests that Vanderbilt already have experience of this phenomenon, which may reassure your father. It is good to be treated at an institution where they have seen something unusual like this before.
sNaPshot is a test for a range of mutations developed at Harvard, as described here:
http://www.guardian.co.uk/science/2011/nov/09/multiple-gene-test-treatm…
best to your dad.
Reply # - January 23, 2013, 05:16 PM
Reply To: Tested positive for 2 mutations
Certain spring: thank you for your reply and the reference to the post about t790m. I did read it and made a reply, hopefully she still checks the site. Trying to locate more information on this, again thank you
Reply # - March 2, 2013, 03:41 PM
Reply To: Tested positive for 2 mutations
calliem3,
You might be interested in this video:
http://cancergrace.org/lung/2013/02/22/inherited-t790m-mutation-oxnard/
and this related site:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-C…
Best hopes,
Craig in PA
Reply # - March 2, 2013, 05:59 PM
Reply To: Tested positive for 2 mutations
Thank you for the posts. I did view them. Dad was positive for the t790m germline. We see the genetics doctor this Tuesday. She will tell us more about it, it's at Vanderbilt and they are partnered up with Dana Farber. I'm glad to help with the research from our end but it still stinks that its my family with this genetic DNA that appears to be harmful. Concerned about my children. This cancer has already taken many people I love. Thanks again for the posts.
Callie.
Reply # - March 3, 2013, 07:15 AM
Reply To: Tested positive for 2 mutations
calliem3,
Yes, I understand, but although it is a bad thing today to inherit it, it might be better news for future generations who unfortunately do have an inherited T790M and know it.
If a person knew at a young age that they had a risk factor for a bad version of lung cancer, they could be hyper-vigilant throughout their life to avoid all exposures to even minor risk factors like 2nd hand tobacco smoke, dust, chemical fumes, pesticide fumes, etc. I assume that not everyone with inherited T790M develops lung cancer.
And since T790M is the most common version of resistance to 1st generation EGFR mutation inhibitor drugs, another 20 years of research might lead to really great ways to control that for years, if caught early enough. Maybe there will even be something targeted very narrowly at just T790M and nothing else (i.e., no significant side effects) that can be used by people with an inherited T790M?
In that sense, your family's participation in that research benefits your descendants and everyone else who is in the same boat. If it the research does achieve what I hope it will in a couple of decades, your descendants should consider you their hero.
Best hopes,
Craig
Reply # - February 6, 2014, 08:24 AM
Reply To: Tested positive for 2 mutations
My mother (soon), her father, and his father died of lung cancer.
What is the first step I should take from a genetic standpoint to help contribute here. All I know is that she is EFGR- . In fact I'm not even sure, since I haven't seen the report, only gotten a verbal from my mom's onco.
(sorry I posted this in the wrong thread, I had too many open).
Reply # - February 6, 2014, 09:04 PM
Reply To: Tested positive for 2 mutations
You can speak with a genetic counselor about the probability that there is a genetic component, though there isn't commonly a significant genetic component compared with the environmental ones like tobacco and other carcinogens. We're more concerned about familial connections in people whose family members died at a relatively young age of the same cancer.
Good luck.
-Dr. West