Topic: P53 Genetic testing

Forum: High Risk for Breast Cancer — Due to family history, genetics, or other factors.

Posted on: Apr 15, 2014 02:13PM

Posted on: Apr 15, 2014 02:13PM

wifessupport wrote:

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

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Apr 15, 2014 02:21PM sarahjane7374 wrote:

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.

Surgery 6/5/2013 Lymph node removal: Left, Right, Sentinel, Underarm/Axillary Surgery 6/5/2013 Prophylactic mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 10/9/2013 Reconstruction (left): Silicone implant; Reconstruction (right): Silicone implant Surgery 11/4/2015 Reconstruction (left); Reconstruction (right)
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Apr 15, 2014 02:25PM wifessupport wrote:

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

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Apr 15, 2014 04:32PM lekker wrote:

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.

Colorectal carcinoma in situ January 2000 (age 30), and now this... Dx 7/2012, ILC, Right, 1cm, Stage IA, Grade 1, 0/2 nodes, ER+/PR+, HER2- Surgery 8/5/2012 Lumpectomy; Lumpectomy (Right) Surgery 10/2/2012 Mastectomy; Mastectomy (Right); Prophylactic mastectomy; Prophylactic mastectomy (Left); Reconstruction (Left): Tissue Expander; Reconstruction (Right): Tissue Expander Surgery 3/11/2013 Reconstruction (Left); Reconstruction (Right) Surgery 4/10/2013
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Apr 15, 2014 05:01PM leaf wrote:

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?

Classic LCIS.If knowledge can create problems, it is not through ignorance that we can solve them- Isaac Asimov Dx 12/8/2005, LCIS, ER+/PR- Surgery 1/24/2006 Lumpectomy: Left Hormonal Therapy 7/15/2006 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Apr 16, 2014 12:17PM kle wrote:

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 

Dx 7/24/2008, DCIS, Right, Stage 0, 0/2 nodes, ER+/PR+, HER2- Dx 7/1/2016, DCIS, Left, Stage 0, 0/1 nodes
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Apr 16, 2014 12:22PM wifessupport wrote:

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.  

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Apr 16, 2014 01:18PM leaf wrote:

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

Classic LCIS.If knowledge can create problems, it is not through ignorance that we can solve them- Isaac Asimov Dx 12/8/2005, LCIS, ER+/PR- Surgery 1/24/2006 Lumpectomy: Left Hormonal Therapy 7/15/2006 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Apr 16, 2014 01:35PM sarahjane7374 wrote:

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. 

Surgery 6/5/2013 Lymph node removal: Left, Right, Sentinel, Underarm/Axillary Surgery 6/5/2013 Prophylactic mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Surgery 10/9/2013 Reconstruction (left): Silicone implant; Reconstruction (right): Silicone implant Surgery 11/4/2015 Reconstruction (left); Reconstruction (right)
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Apr 16, 2014 01:55PM kle wrote:

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    

Dx 7/24/2008, DCIS, Right, Stage 0, 0/2 nodes, ER+/PR+, HER2- Dx 7/1/2016, DCIS, Left, Stage 0, 0/1 nodes
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Apr 16, 2014 02:05PM wifessupport wrote:

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.

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