Genetic Mutation Question

If they have a person with a suspicious family history, then they normally try to do genetic testing on the first person in the family tree who had breast cancer.  (In other words, if a grandmother, mother, and daughter all had breast cancer, and they were all still alive, then they would try to do genetic testing on the grandmother first, if that fits everyone's desires.) This is so they can try to find the mutation in the family.

Once they find the mutation, then it is much easier (and cheaper) to JUST look for that particular mutation at that specific place in the mother and daughter.  If they wanted to look at someone's chance they had this mutation and they didn't have breast cancer, then they would just look at that particular place in the BRCA gene to see if they found the exact same mutation.  So in this case, if the daughter had a sister  (whether or not she had breast cancer)  they would still look for this one mutation. Its a lot easier and cheaper to test if you know what you are looking for.

If your sister has the only breast and/or ovarian cancer in the family,  then (assuming you and your sister have the same parents - i.e. you aren't half sisters, and none were adopted) then you didn't get her mutation - because she didn't have one.

It is theoretically possible, though the chances of this happening are like 1 in a zillion, that a cosmic ray could have struck your mother's ovaries and hit exactly the right gene to cause a mutation which you might pass on to your children, so theoretically you could have a BRCA mutation that you could pass on to your children.  But, again, the chances of this are astronomically small.  

Only about 10% of breast cancers are associated with known genetic mutations. They will probably discover other mutations in the BRCA gene  , and other gene mutations that are associated with hereditary breast cancer in the future.  There is one, for example, the PTEN group, that is associated with an increased chance of breast cancer.  But there have only been about 300 people worldwide - ever to have been diagnosed with this- so these other gene mutations in other genes are very rare.  (PTEN 'only' puts you at about 25% breast cancer risk anyway, which is about the risk of a person with atypical hyperplasia.)

So, we may find more information in the future, but that's all the  genetic testing we can do for now for BRCA genes. 

That's what I understand, anyways. 

It is good that you are being followed closely.   Your sister is so lucky to have a sister like you who cares about her, and a sister who is trying to take care of herself!

Best wishes to you and your sisters.  Tell your sister about this website, if she is interested in on-line support. No matter what your sister is going through, or what her diagnosis, there is probably someone here who has gone through something similar.

We do know that women who are BRCA positive tend to have premenopausal (or earlier) breast cancer or ovarian cancer.  We don't know that about the other known mutations (such at PTEN) because the incidence is so low.

There are almost certainly other single-mutation genes out there that put you at higher risk for breast cancer.  But we don't know where in a person's lifetime they tend to cause cancer.  This could be different for different genes or different mutations.

Hi Shelt.

I'm so glad your sister is in strong recovery mode, and that you are both being so proactive with your hereditary cancer concerns.

Of the percentage of hereditary breast and ovarian cancers, my understanding is that most are actually neither BRCA1 nor BRCA2.  Most unfortunately remain in the 'cause unknown' category.  With your concerns I would strongly urge you to speak with a registered genetic counsellor who is fully versed in these dynamics and has the training and experience in this area to guide you through possible testing and treatment options.

I can appreciate this is an unsettled time, considering what your sister has gone through at such a young age and your also feeling a cyst concern.  With this I'm a bit surprised your physician authorized mammography prior to at least age 30.  There are strong (preventative) reasons for not having this done at a young age, as it involves radiation and on still developing breasts.  Another option is FDA-approved breast thermography.  Baselines for this are recommended starting at age 20 and then annually after that, and later in tandem with mammography.  It's important to get a thermographic facility referral through a compounding pharmacy to ensure the related technicians are well-trained.  (I personally hope that someday there is a full replacement for the mammography radiographic tool being used on those with high risk for breast cancer.)

No matter which route you choose, I wish both you and your sister the very best.

Kim:

 I was very interested and also very, very sorry to read your post - this is actually the first time that I have been on this forum.  I also had three sisters and a brother.  I am fortunate in that I still have two of my sisters living.  I lost one sister to ovarian cancer at age 54 (9 years ago) and my brother at age 56 although he did not have cancer (it ws a pulmonary embulism.  Of the 3 sisters remaining we have all had breast cancer.    I was just diagnosed in Septermber with a recurrence after 9 yeasrs.  I just had genetic testing done and they have indicated in the BRACA2 there is something of uncertain significance.  From what I can understand reading the report and I am not at all familiar with what they are saying, this is the" first observation of this variant in unrelaed families and and on families have been tested for this variant  or some such thing.  Anyhow they want to test family members who were diagnosed prior to 60 years of age.  I really don't know what if anything this means and I have not yet spoken to a geneticist as I had the testing done through my Breast surgeons office.  My nieces prior testing showed negative although I was told that she probably didn't have as comprehensive a test as I did.

Annie/britannia

Mutd - thanks for the good information.  The variant is F1421L (4489T>C).  Haven't had a chance to speak to anyone about it yet.  Am getting reading for my surgery on Friday.  As you say, I am doing the BM because of the recurrence, not because of the test result.  Family history was another reason to get the good breast removed.  I believe I mislead you as far as my niece - it is amazing how an apostrophe changes the sense isn't it?  I was trying to say the result of the GT my niece had showed up negative in BCRA1 and 2.  I am sure it was after her mastectomy but she did need chemo and I am not sure if it was before she started her treatments or not. .  The reason I am a little vague is that she lives in England and four weeks after her mastectomy she suffered a stroke (caused by a blood clot from a congenital heart defect they weren't aware of) also everything was done over there where they do things a little differently.  I spoke to a LAB over there that is a partner of the lab over here and she mentioned they probably didn't do as extensive a test on her. We now have to make the arrangements to have her and her mother tested.  

Hi ladies, I was reading some of what Shelt had to say and the replys.  Dec. 23, 1999 at 34 y/o I felt my first "cyst" and had a mamogram and ultrasound and it was a cyst, the only thing is the tests showed multiple cysts - all different shapes sizes, and different fluid filled lines. (i'm a nurse so when I saw something strange I asked and they couldn't hide it from because I already saw the screen or the x-ray.  Any way over the years, the cysts multiplied (from a c bra cup on the right to an E size cup and the left breast C cup to DD).  The new study out for women with known breast cancers in the family history and someone with cysts like mine, they do an MRI.  The only problem with an MRI is "it throws up too many flags"  it's hard to tell sometimes the difference between cyst and masses.  I have several biopsies all of which were negative.  I've had atypical hyperplasia cells during this whole time.There was an area on the MRI that really concerned the doctors so they did a surggical biopsy.  My doctor is very thorough and he got some extra tissue and that was where the DIC was found with atypical hyperplasia cells.  They originally told me everything looked negative because it was an aginoma sitting in a solid cyst.  I was told I would never get any kind of breast cancer because it is all on my dad's side. HHHMMMMM.  I had radiation and worked then I started developin the cysts again especially in the left breast and had to have another biopsy - atypical hyperplasia cells.  I didn't want the gene test because of insurance payments.  We did all the tests as if I carried the gene they were all elevated but have come back down to normal.  I had bilateral mastectomies with reconstruction and still going through that and now have develope anemia and problems with my stomach.  I'm doing the gene testing November 25 at my doctor's request.  The genetic consultant was wonderful.  I am more tired now than I've ever been.  What does all this mean to me?  Only God knows what we will or do have.  It's up to us to be pro-active and take care of ourselves and our families.  As one of the other ladies said "Knowledge is Power.  I hope you are all ok and remeber the saying, God doesn't give us more than we can handle.  Just think if it was someone else going through this that couldn't handle it.

I will be the first one to ever be tested.  I'll have the test done on 11-25-08.

just fyi...there is a good website for information on genetic cancer at facingourrisk.org.

Niki, yes, there is still a lot unknown variants, sometimes as many as one "unknown" test result for every two or three positives (and it may be even worse in minority groups which aren't yet studied as thoroughly). But over time, more and more uncertain variants become certain (and most of them actually become benign).

 You probably should have based your decision just on family history alone, and not using the variant result (if there were no alarming signs about your variant). Of course the fact that both your mother and your sister had it, it sounds suspicious ... but there is 25% probability of it happening just by chance even if the variant is benign. Which variant was it, by the way?