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P53 Genetic testing

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wifessupport
wifessupport Member Posts: 6
edited October 2021 in High Risk for Breast Cancer

Hi All,

My wife's oncologist is suggesting that my wife get checked for P53 mutation after her local recurrence.  Can anybody please shed any light on that?  She is negative for BRCA1 and BRCA2.   Is it really necessary to get this done or is it something we get it done and worry about it without any solution?

Thanks

Comments

  • sarahjane7374
    sarahjane7374 Member Posts: 23
    edited April 2014
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    My sister was dx at age 28 with IDC.  My BS and genetic counselor felt it was appropriate for her to be tested for P53 mutation and recommended I ask her to get it done.  The reasoning was her young age at dx and because we have a very limited known family history.  P53 mutations can cause Li Fraumeini syndrome which pre-disposes the bearer to multiple cancers (including BC) and typically results in early onset cancers. 

    My sister tested negative for P53 (and BRCA negative).

    Has your wife seen a genetic counselor?  They may be able to provide you with a better explanation.

  • wifessupport
    wifessupport Member Posts: 6
    edited April 2014
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    My wife saw a genetic counselor in October last year, at that time they said, they do p53 testing for patients who have had BC below 35 years of age.  My wife had it when she was 35, so they said it is very rare that she will test positive.  So we did not worry about it.  However, she had a local recurrence in January and she is due to get radiation next month.  The oncologist says the dosage of radiation and whether she will get radiation or not, will be determined by P53 test.  Has anyone had this being told to them?

    Thanks

  • lekker
    lekker Member Posts: 238
    edited April 2014
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    A germline mutation in TP53 is very rare, but there must be enough of a suspicion for your wife's genetic counselor to want the test.  Ionizing radiation (either diagnostic or therapeutic) might not be as effective - or might cause more damage - for someone with this mutation.  I doubt many people on this site have had to deal with this issue as not many people in the world carry the mutation.  But not many young women have recurrent breast cancer either.  I think it's great that her team wants to investigate this even if there's just a small possibility.  By confirming she doesn't carry a mutation, they can go ahead with radiation.

  • leaf
    leaf Member Posts: 1,821
    edited April 2014
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    This abstract seems to suggest that p53 deficient cancers may tend to metastasize more. http://www.ncbi.nlm.nih.gov/pubmed/24658082

    In this study, 1 out of the 3 (obviously a very small sample size) p53 mutation carriers was 44 years old. http://www.ncbi.nlm.nih.gov/pubmed/23580068

    and in this abstract they had a person with an onset of IDC at age 47 and a family history of late-onset (age 67, 70) cancers. http://www.ncbi.nlm.nih.gov/pubmed/23667851

    To me, it sounds like p53 mutations are found in about 1/2 of human cancers.


    TP53 is a tumour suppressor gene that causes Li-Fraumeni
    syndrome and affects adults and children. This highly penetrant gene
    predisposes for a wide spectrum of tumours, including sarcomas,
    adrenocortical carcinomas, brain cancer, and very early onset breast
    cancer [39, 40]. Most cancers are manifested from birth through late adulthood [39]. TP53 mutation carriers face a lifetime cancer risk that exceeds 90% [4042], while the clinical benefit of extensive surveillance of these individuals remains uncertain [43].

    Patients
    with Li-Fraumeni syndrome have an abnormal response to low-dose
    radiation that should be avoided as a therapeutic approach because of
    the increased secondary tumour risk [44].

    Breast cancer is the most frequent malignancy among female TP53 mutation carriers, with approximately 5% of these cases being diagnosed before the age of 30 [39]. While Li-Fraumeni syndrome accounts for a small fraction of breast cancer cases (~0.1%), TP53 mutation
    carriers have from an 18- to 60-fold increased risk for early onset
    breast cancer (diagnosed before the age of 45) when compared to the
    general population [4548].

    ww.ncbi.nlm.nih.gov/pmc/articles/PMC3618918/

      Would this be worth another discussion with a genetics counselor?

  • kle
    kle Member Posts: 9
    edited April 2014
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    HI,

    I have a question for you .   I have a different scenerio, and a genetic's counselor has spoken to me about the TP53 test. I've had multiple cancer's that are radiation induced.   But I have no family history, and wonderded if your wife has a family history of cancer ( seems that this is common for Li-Fraumeni).     From my understanding if you have the mutation, then the upcoming radiation could be affected by this.

    KLE 

  • wifessupport
    wifessupport Member Posts: 6
    edited April 2014
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    Well my wife's family has no history of cancer.  She has only one in extended family with ovarian cancer.  When we spoke with the counselor last time in October, they said it is not even considered close and hence family history was ruled out.  They just want to check P53 because she had a recurrence within 4 months of treatment. Her perception treatment ended in August and she was diagnosed with local recurrence in January.  

  • leaf
    leaf Member Posts: 1,821
    edited April 2014
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    To me, it sounds like some women with early onset breast cancer can be at risk for a p53 mutation even if they have no significant family history of cancer. It sounds to me like if she is positive for a p53 mutation that this could really affect her care.

    The potential implications of multi-gene assessments of individuals at
    increased cancer risk, which have already begun to identify individuals
    with very little personal or family cancer history carrying germline TP53 mutations, are considered.  
    http://www.ncbi.nlm.nih.gov/pubmed/24706533

    This paper looked at women under 30 (I understand your wife was over this age at diagnosis)

    By reviewing similar data published between 2000 and 2011, we estimate
    that 5-8 % of women diagnosed with early-onset breast cancer, and who
    have a negative family history,
    may have a mutation in the TP53 gene. 
    http://www.ncbi.nlm.nih.gov/pubmed/22851211 (emphasis mine)

    This 26 year old apparently had a de-novo p53 mutation. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X.   http://www.ncbi.nlm.nih.gov/pubmed/21225465

  • sarahjane7374
    sarahjane7374 Member Posts: 23
    edited April 2014
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    In the report from my genetic counseling appointment, it was noted that they recommended testing for my sister due to her age at dx, and that based on the limited family history that we had knowledge of, the p53 mutation, if present, would likely have been de-novo. 

  • kle
    kle Member Posts: 9
    edited April 2014
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    I would think this would be important to know if she has it , for her upcoming treatment...but I would want more clarification of why with her history they are thinking that.  Does the oncologist think just the recurrence, or are there more red flags.  I've read you can "start" the mutation  yourself., it is not "only" genetic.  If the oncologist makes a case that you can believe in, maybe it will make sense to do the test.  I'm not sure how strong a case for the test the "recurrence"  only is ....you'd have to ask the experts.  

    For me, I have no upcomig treatment, so my case is different from your wife's.     

    KLE    

  • wifessupport
    wifessupport Member Posts: 6
    edited April 2014
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    They are making this recommendation based on the fact that she had a quick recurrence.  She was diagnosed at 35+ first time. I have read about many women on this board who had a quick recurrence and not done p53.  So I am not sure whether to get it done or not.

  • vyneza
    vyneza Member Posts: 1
    edited July 2014
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    I know that this thread is a few months old but I felt compelled to contribute. My identical twin sister (age 34) was diagnosed with breast cancer (Stage 2A) in November. She lives in Boston and they told us the protocol they're trying to implement for women under the age of 40 is to test for BRCA1/BRCA2 first, if that is negative then test for Li-Fraumeni (TP53 mutation). 

    Their reasoning is that for young women diagnosed with breast cancer the culprit is more likely to be a genetic mutation which would affect treatment options.  They're also trying to include testing for Li-Fraumeni because they think it is more prevalent than previously thought 1 in 5,000-20,000 people.

    We have no family history of cancer except for our maternal grandmother who died from ovarian cancer. So the genetic counselor was pretty convinced my sister may test positive for BRCA1/2 and was also equally convinced especially with our lack of family history she'd be negative for Li-Fraumeni. 

    It was a such a sigh of relief when her BRCA1/BRCA2 results were negative, we didn't think twice about the TP53 test. We were sure it would be negative. Well....that turned out to be wrong. My sister was positive for Li-Fraumeni, I subsequently got tested and am positive as well. 

    We are a de novo mutation and though knowing the results has been a blessing and a curse.  For us it was better to know than not know because it greatly affected my sister's treatment options. Double mastectomy versus lumpectomy and no radiation versus radiation. We're also following the recommended Toronto Protocol surveillance which helps people with Li-Fraumeni find their cancers at their earliest stages when they're easier to treat.

    I know our case is different but it may sound like in the case of your wife, the doctors are trying to cover all the bases to understand why there was a reoccurrence especially so soon after treatment. 

  • wifessupport
    wifessupport Member Posts: 6
    edited July 2014
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    Thanks Vyneza,

    In my wife's case it was negative.  It was used more for deciding treatment options.  If it was positive they were hesitating to give radiation treatment.

    Thanks

  • mommy13
    mommy13 Member Posts: 13
    edited January 2015
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    I also have Li Fraumeni. I will find out in a couple weeks if my parents have it or not.

    I felt the same as you, so relieved I was negative for the other gene. And the counselor was seemed so positive Id be negative for this. Guess not.

    I am also following Toronto protocol. I was diagnosed one month after doing 25 rounds of rads..... :/

    I have a 5 year old and 1 year old I have to have tested :(


    It's a terrible thing.

  • Flautalee
    Flautalee Member Posts: 46
    edited January 2015
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    Vyneza,

    What is the Li Fraumeni mutation? When I had genetic testing (for the third time, as the testing became increasingly sophisticated) in 2011, I was still negative for everything. Do you know when that mutation was discovered?

    I hope that you and your twin are doing well and thank you for sharing your experiences and knowledge.

  • Flautalee
    Flautalee Member Posts: 46
    edited January 2015
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    Vyneza,

    What is the Li Fraumeni mutation? When I had genetic testing (for the third time, as the testing became increasingly sophisticated) in 2011, I was still negative for everything. Do you know when that mutation was discovered?

    I hope that you and your twin are doing well and thank you for sharing your experiences and knowledge.

  • elabee
    elabee Member Posts: 6
    edited March 2015
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    Flautalee, I noticed your post from January 2015 regarding Li-Fraumeni syndrome. It's a cancer syndrome that was discovered in the 60's. Back then, Li-Fraumeni syndrome was diagnosed based on having an extensive family history of cancer.

    More recently, a tp53 mutation and/or extensive family history is associated with Li-Fraumeni syndrome. Women get tested for this mutation if they develop breast cancer under the age of 35 and are negative for the BRCA mutation.

  • sas-schatzi
    sas-schatzi Member Posts: 15,879
    edited June 2015
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    This is a repost from my social thread. I was trying to find something else. Thought I'd drop the link off. The thread is inactive, but just maybe some  of you are still around.

    My friend brought a link re: KRAS. I haven't researched it yet.

    link to a KRAS article: http://discovermagazine.com/2014/dec/16-true-believer

    Repost:

    Thanks, not sure if I've read about that particular gene. I have thought that I should be tested for Chek2 and Pten after allot of research about 3 years ago. What's very cool is Farmerlucy started a thread. She identified Color Genomics(CG). It was started by a group of folks after Myriad lost their court case for Brca patent. This group felt that genetic testing could be made available for a llot less than what other companies charged.

    CG charges only 249.00$ and tests for 19 different genetic errors. Inclusive of the Brca's. I tried to C&P a list and couldn't. This link is to a page that has a box with each listed. Put the cursor over each one. A box will drop down with an explanation of what the gene is related too.  https://getcolor.com/learn/the-science  You don't need a doctor order. But some have been able to work through getting the doc order and insurance coverage. I haven't gotten around to that b/c I forgot.

    I checked the list and Kras isn't on it.

    -------------------------------------------------

    I went back and did a relook on Color genomics. The drop down box for each listing what the test identifies is not complete. Someone else here on BCO had a complete box of all the genetic tests and what cancers they are related to, if I find it I'll drop it off.


     

  • farmerlucy
    farmerlucy Member Posts: 596
    edited June 2015
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    Sas - here is the link you were looking for (I think).

    https://www.myriadpro.com/myrisk/why-myriad-myrisk...

    FYI I'm still waiting for the results from Color Genomics. It has been about eight weeks and they said six to twelve.

  • sas-schatzi
    sas-schatzi Member Posts: 15,879
    edited June 2015
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    Lucy Hi and thanks, it's not the list, but this is a very good list for sure. The one on Color Genomics has 19 --good. The drop down explanation boxes don't have complete info. Not sure if it were side by side like this list how it would compare. Colors has to many --Etc.'s-- Hmm, I'm interested in the ETC's.  I didn't catch that till today.

    My 2nd primary is thyroid cancer. Myriad doesn't list thyroid as a column

    In the biggy cancer stat publication from I think CDC, it's covering stats from 1977 to 2012. Thyroid cancer has increased almost in every state. I have this bigwig thyroid doc @ Moffitt CC in Tampa. They've hired extra staff. No one knows why there is the big change in thyroid c. There's lot's of surmising, but really no clue.

    Lucy will you Pm me if you remember when you get your Colors test results? I would like to hear how they handle the whole thing. Also, if your TP 53 comes back positive. Don't let it wig you out. They will talk Li Fraumini.(sic). But the way the thyroid doc explained it when I said I was worried about it, WAS---it's a chicken and egg thing. It can be a primary genetic break and if it's done after cancer dx'd it most likely will be positive. That was the first time I heard that. Didn't press him for more info. Seemed reasonable. If you look at the Myriad chart it's positive for every cancer. Seems even more reasonable.

    Personally on the thyroid cancer, I would like to see a study that takes a large sample of patients and looks at their radiation history over the long term. One CT= 200 chest x-rays. I have seen a different ='s on the CT and CXR. My number is from a radioloy study from the national radiology board in 2006. A Pet includes a CT--not sure how much radiation we are getting with that one. Then the old dental x-rays. Go figure, who knew we were increasing our risk by being diligent on teeth care. Our radiation exposure has skyrocketed from the 1980's. Never had a thyroid guard for any of the CT's that I remember.

    I'll see if I can't locate the CDC stats graph thingy. It's really interesting to look at each state.

    Thanks again for posting the Myraid chart. Take care, sassy 

    This link is to a very cherry article about thyroid cancer risk.

    http://thyroid.about.com/od/thyroidcancer/a/secondcancer.htm

    The SEER stats 1975 to 2012. You  have to play with the parameters a bit

    http://seer.cancer.gov/csr/1975_2012/browse_csr.php

     

  • TectonicShift
    TectonicShift Member Posts: 102
    edited July 2020
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    .

  • Kelhab
    Kelhab Member Posts: 7
    edited September 2021
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    hi i was also told i have li freamini i would love if you can reach out this is all so scary

  • 2019whatayear
    2019whatayear Member Posts: 468
    edited September 2021
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    There is an org for people who have genetic mutations that increase cancers, it’s called FORCE the website is facingourrisk.org . There is also an active FB group - :-) big huga

  • manal42
    manal42 Member Posts: 3
    edited October 2021
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    I guess there might be a tumor mutation without Germline mutation ...I mean there is only mutation in the tumor ....it is not inherited

    Patients with Germline mutation in breast cancer are more susceptible to radiation side effects ...they are usually offered the proton radiotherapy ...we have a strong family history for breast cancer ...and we had the same advise too ...best wishes for your wife ...