Getting BRCA test when no one else in family is tested

kibbles, here's the problem that I believe your doctor is considering.  While the BRCA genetic mutation is the most well known inherited gene that increases one's risk of BC and ovarian cancer, without a doubt it's not the only one.  A couple of other genes are already known and there likely are other genes that are yet to be discovered.  Additionally, there probably are other genetic factors - different than gene mutations -  that could be inherited that lead to a increased risk.   For example, there is a lot of cancer in my family but I don't carry the BRCA genetic mutation.  So maybe there's another gene that's causing all this.  Or maybe the link between my mother and me (we've both had BC) is that we both have extremely dense breast tissue, which is a major risk factor for developing BC - and I probably inherited that from my mother.

So if your family members who've had BC and/or ovarian cancer had been tested and if it was known that the BRCA genetic mutation is in the family, then if you tested negative, you would know for sure that you don't have the same risks.  The cause of their cancers would be understood, and you would know that you didn't inherit it.  But without your other family members being tested, you don't know what has caused their cancers.  So if you test negative for the BRCA genetic mutation, you won't really know if you are lower risk or not.  Maybe it was the BRCA gene that caused their cancers, but maybe it was something else.  And if it was something else, then you could still be at high risk.

On the other hand, of course, if you test positive, then you will know that you are at risk and you will be able to take action.  So I'm not suggesting that testing might not make sense for you; the issue however is that because your other family members who've had breast and ovarian cancer haven't been tested, a negative result may not give you the reassurance that you would want.  

Does that help explain what your surgeon said?  My suggestion is that you talk to a genetic counsellor - someone who is an expert on this.  He or she can explain it much better than your surgeon (and me).  He or she can explain the implications to you and your family members, if you test positive and if you test negative.  He or she can also advise, based on your family history,  whether it makes sense to take the BRCA test or not.  Then you can decide what you want to do.

I hope this helps!

Hi,

 I just wanted to say I was also tested and came back neg but I remember my doctor saying that a patient was tested and came back neg then tested again after ten years and was positive. This was because the tests had improved.

 I take my result as being negative at this moment in time awaiting further research.

My family were also all in their early 40's

Best wishes...

Kibbles, it is a standard recommendation to start testing in a family from the highest-risk individuals (the ones most likely to have a mutation, which means both personal and family history of cancer). But it isn't always possible to start there. Some high risk relatives may be dead, other may lack good insurance coverage, and some may simply be unwilling to do it, or even keep their results secret.

 So lower-risk women are also getting first tests in their families, and with it comes the risk of uninformative negative results. "Uninformative" doesn't mean that the result leaves your predicted risk unchanged. Any negative result makes it less likely that you will develop cancer. Exactly how much less, depends on your family history, and a Genetic Counsellor may help you eveluate it. But "uninformative" result always leaves open a small possibility that there is some unusual, presently undetectable mutation in the family. And therefore your predicted risk doesn't drop as much as for the women with "true" negative results.

 Ruby, an important note about the free test for your mother. Usually the free tests for "uncertain" variants are just that, tests for just one particular variant. The rest of the two genes is not tested. Therefore, your mother will learn if you two share the same uncertain variant, but she won't know if there is a true mutation somewhere else in her genes. Not until she takes the full test, which probably won't be free. 

Came back negative for BRCA....so my daughters will not inherit from me......maybe father....but not me.

My mother has not been tested and she has 5 other daughters. My mother was triple negative. I told my sisters that there is no proof that they are positive or negative. If my mother would get tested at least we would know if she was positive and my other sisters could decide if they want to be tested.

I am also waiting for a distant relative to get some medical information 1st hand when she attends a family reunion this weekend. Some of the women have died of breast cancer from my great aunt's family descendants. There was some 1st degree cousins who died in their 30's and I have confirmed one of them had breast cancer and today her daughter has breast cancer. So I am really interested in finding out about the other 2 young women who passed in their 30's. Hope she has luck in gathering information.

Terry 

Ruby, the test for a specific variant is about 10 times less expensive than a "complete" test, that's correct.

 Maybe that's why it is given away for free for some relatives in the families with "uncertain variants". Your mother will get it for free anyway, if you don't count an appointment to draw blood, and possibly a follow-up with a genetic counselor. But this freebie isn't going to be a very useful test for you and the rest of the family yet. And neither are the $300 tests which could be ordered by the relatives not eligible for free testing. Not fully useful at least until the lab has enough results to prove that the variant is benign (or not).

That's what the "uncertain" label really means, "do not use it for making clinical decisions yet, because it isn't yet perfectly clear if this is a mutation or a normal variation". "Not perfectly clear" doesn't mean you are completely in the dark, of course. 15 other families have the same variant, so something may already be known about it (What is the variant name? Have you searched the Internet for it? What did the lab say about their results to date?)

And more data may be on the way ... in your family, for example if your mother doesn't have it, then you'd think that it's probably benign, right?

Kibbles SO sorry to hijack thread. All my best to you as you make your decision.

This cancer stuff messes with the mind and sends me off on tangents.

Hello All

If you would be kind enough to give me some info.

Should I have the test or should my daughters? how useful will it be?

There is bc in the family -my fathers sister and his mother died of liver cancer which may have been a met from BC we dont know -and my father died of a blood cancer

Best regards to all 

Anna

 Mutd

Thanks.Hope all goes well for you 

Anna

ok, I have held off,not sure what to say-but now I will tell my story. My great-grandfather died of stomach cancer. He had 2 daughters-1 died in her forties-no one seemed sure why. His other daughter-my grandmother -was in her 70's with no cancer. Out of nowhere, my mother was diagnosed stage 4 BC. She had no risk factors that we knew of (this was in 1979)  and we were so confused. She was postmenopausal and had had a hyterectomy.

She died in 1981, age 59. Shortly thereafter, her sister was dxed w/ ovca. Still no connection (no gene testing yet available). No other family history. My ob/gyn tells me not to worry-different unrelated cancers. Grandma dies of pneumonia at 93.

fast forward to 2000. My younger sister is diagnosed w/ melanoma. Another "unrelated" cancer.My new pcp tells me about brca and suggests that family history may indicate it. If it were not for my aunt w/ ovca,they would have thought my mother's was sporadic. I decline the test, but am watched carefully. I did not consider this a strong history. According to Myriad's online calculator, I had a 5% chance of being positive, they do not recommend testing unless you are 10% at risk.

2008-I need a biopsy!!! (post-menopausal, mind you). I rethink the testing thing for my daughter's sake,sure that I will be negative, but wanting the assurance in a test result. Mind you, all these people are dead now-including 2 of my mother's brothers who also died of stomach cancer(unrelated, right?). No one has been tested, still they now recommend it for me. Lo and behold, I am brca2+. That was a shock and sent me reeling for months. It is NOT just a piece of information-it is life-changing. I could easily have been an uninformed neg.-good thing I took the test!

You could be uninformative neg-what would you do, considering your history? You could be positive-what would you do? This is heavy information. I really don't understand why they counseled your mom against it either. Were you two seen by a Certified Genetics Counselor? Not nurse oncologist, surgeon or oncologist-REAL, GENUINE, Board-certifed CGC?

Well, I hope you are able to decide what to do, and if you get tested, what to do with the results.

Good luck!

Kibbles, I face the same riddle, too wild a combination of different cancer types in the family to make sense, genetically.

 But Tweekerbeeker, your story looks a lot more like a BRCA mutation in the family. And Myriad's model would underestimate risk in your family, you really need a better model. And finally 10% risk threshold is obsolete, nobody is setting the level so high anymore!

So in case if you want to reopen the case with a Genetic Counselor, please note the following:

 1. Great grandparent's stomach cancer is important. Who knows what changed with our environment in the last century, maybe our food got safer, but anecdotally, in those days people in BRCA families were often coming down with "stomach cancers". Today, there isn't much of increase in stomach cancer rate in BRCA+ patients anymore, and most of today's risk models ignore stomach cancer. But three generations back, it mattered.

2. Grandmother without cancer. If she had ooph / hyst (like many women in the older generations), then her risk of breast / ovarian cancer would have been much lower, and even with a mutation she could have made it to her 70s.

3. Mother with br ca after 50. Most models would play down the risk if your relative had breast ca after 50, but remember, she already had ooph / hyst, and therefore her br ca risk went down, cut in half. Unfortunately the more simple models don't take oophorectomy into account. So even if she was in mid 50s, it is still significant. 

4. Ovarian is, obviously, connected. But so is melanoma. Its rate increases quite significantly in BRCA carriers, but it remains a rare disease and therefore many models ignore it.

5. "10% probability" "rule", the risk of "uninformative negative" result, and why neither is right. The "10% rule" is mostly just a ballpark value which the insurance companies apply to new and experimental tests. They wouldn't pay if there is a great chance (90%+) of a negative result.

But BRCA1/2 test isn't new, or experimental. And testing would miss the majority of the mutation carriers if the "10% rule" still applied. So today, almost everybody agrees that women with smaller risk should still be allowed to get tests. (The disagreement mostly comes from the socialized medicine nations like Canada or UK, where the government restricts and rations the tests, and the lower-risk sisters end up with a short stick).

The danger of "uninformative negative" results is proportionally almost the same in all risk groups. That's because most "uninformative" families also have BRCA mutations, but of a few rare and unusual types which may not be detected by conventional tests. As many as 10% of mutations may be hard to detect (it depends on how modern is the test). If you're very likely to have a mutation, then the chance of "undetectable mutation" is also higher. But if they predict that you have only 5% chance of having a mutation, then the risk of "invisible mutation" goes proportionally lower too, to one half of one % or less. Would you worry about something so unlikely to happen?

What is likely to happen is an "uncertain" test result. Some genetic variant which may or may not have connection with cancer. As many as 3, 4, or 5% of all BRCA tests have "uncertain" results. It may take years for the geneticists to pinpoint the connection between a variant and cancer, and most of us are very uncomfortable with this uncertainty dragging on for years. If you can't stomach the uncertain result, you probably shouldn't be tested if your risk of having a mutation is below 5%, because if it is any lower, you just might face a greater probability of uncertain result than of positive result?

But in the end, the right "percentage threshold" is rooted first and foremost in your psychology. Some women won't get tested even with 50% chance of having a mutation, and they really like uncertainty. But for others, if there remains a stone unturned, it nags them. You need to look into your own personality and decide. A genetic counselor may guide you, but may not give you any orders.

Hi, new here, not sure if this helps answer anyone; just my own experience. If you can get in to see a good genetic counselor, you can get some insight into all the different risk groups.  I was offered and took the BRCA but was negative.  My sister had endometrial CA and she was tested for and her tumor was positive for Lynch syndrome, which also increases the bc risk (recently added to list), colon CA risk, melanoma, ovarian, stomach and a bunch of others.  I am now treated as if I have the Lynch mutation also, which qualifies me for more frequent stomach, colon and other tests.  Not very convenient, but the benefits are the likelihood of earlier detection and better survival.  Mom died of bc at age 60 (dx at 43), we thought DES related (she took with 6 kids). CA (kidney, endometrial, breast) showed up in three oldest of her children.  My dad is living, has had prostate CA.  Mom's parents lived into their late 90's and died of stroke, all of their many siblings same--two lived to be 102.  Father's parents died young of cardiac.  Neither of my parents had siblings.  No one knows who brought on the mutation.

Susan Love's Breast Book has a good explanation of all this; it helped me understand.

I hope this helps someone. 

 C

Floridian - one reason to consider BRCA testing for you would be that a positive result may lead you to consider preventative surgery, especially for the ovaries.  Unfortunately no reliable screen exists for ovarian cancer at this time.  The CA125 is the best that is available, but is not sufficiently effective.  Because of this most doctors recommend that BRCA+ women seriously consider removing the ovaries at approx. age 40.....ovarian cancer is deadly!  Surveillance for breast cancer, while not perfect, is much more reliable......

Oh, I see, Cbm, so she hasn't got the genetic mutation test, just a tumor test. I am a bit queasy about going into too many details about Lynch syndrome in this forum and this thread. But its genetic story also has its uninformative-negative issues, so I will try. Or we can switch over to http://www.facingourrisk.org forums (they are also focused more on breast cancer, but also on ovarian and generally all types of inherited cancer, including Lynch a.k.a. HNPCC syndrome).

 HNPCC genes are also involved in repairing DNA damage, like BRCA genes, but in a different part of the cell's "repair shop". HNPCC genes do their work in teams of two (as "protein dimers"), the most important pairs being MLH1+PMS2 and MSH2+MSH6. When a tumor is tested, one of the two things is checked (or both). One is the instability of certain mutation-prone locations in the chromosome. It is a tumor DNA test. If it is positive (so called "MSI high") then a repair deficiency is suspected, most probably due to Lynch. But which gene's broke is anyone's guess. Another type of tumor test is staining for specific proteins called IHC. In most Lynch syndrome tumors, two repair proteins would be missing (the product of the gene which was broken in the first place, and its team mate which was left alone and became unstable). So if IHC is negative, then it is more or less clear that a mutation lurked in one of the two genes.

MSI high or IHC- are still short of finding the mutation in a family. Although these kinds of test results hint at a Lynch mutation so strongly that Amsterdam family history criteria may no longer be important. But the existing gene tests don't look at all HNPCC genes (only the 3 or 4 most important ones), and they don't detect all types of mutations (only the most common types), so the risk of uninformative negative results may be even stronger in the case of HNPCC genes

AnnieG and then Donna (Vtartist) wrote about Lynch syndrome on facingourrisk.org main board (both of them have BRCA mutations too, which is a real quandary).

http://www.facingourrisk.org/messageboard/viewforum.php?f=3

Anyway, while you are still looking what good might be there on their site, I just add a few words here. Sorry for OT. I never quite understood the meaning of this "lifetime risk" percentages, even though I was absolutely into math in high school LOL ... but my Mom talked me out of majoring in math, like "you don't wanna end up with a boring computer programing job like Dad's" (really! I got to learn stuff about DNA instead). Anyway, what's the real use of "lifetime"? Do I really plan to live into the 80s, Alzheimer and all? I would need the risk breakdown by age. What's in store in my next 5, 10 years. It's one thing to have 80% lifetime risk with the median age of disease at 65. Quite a different thing if the median age is 40 and the first quartile is 30!

And on the topic of hMSH2 / hMSH6 ("h" stands for "human" BTW, as if we had any other species genes to the rescue). If they are missing from your sister's MSI+ tumor, then she really wouldn't even need a genetic test to plan her treatment / surveillance / prevention. Just treat it as Lynch syndrome. But to clear any doubts, and especially to help you understand your own risk, it would be better to look for the mutation responsible for it all. Both genes are routinely tested for mutations by several labs. Myriad Genetics (better known for BRCA tests) is one of them.

Nothing dumb about it. There are genes and gene variants in your body, in your family, and in the tumors, and the story changes according to the settings. But everybody uses the same acronym, like BRCA1 or MSH2, so it's easy to be confused.

And BTW we are getting back on topic, right? About pros and cons of getting a genetic test when no one else in the family had it.

In the family: the classic hereditary cancer syndrome picture is a family and a mutation which hails from many generations back. So far back, in fact, that it looks like it was there in all generations. The mutation is technically "autosomal dominant" which means that it is passed, on average, to every other son and daughter, and predisposes them to cancer.

Why "every other"? Because each of us has two copies of the gene (one from each parent). Only one of these copies, randomly selected, goes to each child. Sometimes a good copy, sometimes a mutated copy.

Why cancer, if one normal copy of the gene is always there? Because in addition to inherited mutations, there are also "somatic" mutations hitting random cells of your body as it grows older ("soma" means body). If a somatic mutation damages an important gene (say BRCA1 or MSH2), it should be perfectly fine, because there is a second "backup" copy of the gene. Except if the "backup" copy is already disabled by inherited mutation, then the somatic mutation breaks the last remaining copy of the gene. And DNA repair system, which struggled to prevent somatic mutations from happening, is now out of order. More somatic mutations flood the genes, and that's cancer.

Therefore, tumors and blood DNA are tested for two different things. In tumors, you expect both copies of the gene to be broken. Often, it can be detected by staining for the protein encoded by the gene. No working genes -> probably no protein is made -> no staining.

In the rest of our bodies, there might be a hereditary mutation, but the 2nd copy of the gene is working fine, and it makes protein just fine. Everything is normal, until a fateful somatic mutation strikes the 2nd copy in some wrong place. But a gene test could see the mutation. It is typically a blood test (our red blood cells don't have any DNA, they jettison their chromosomes to become more slim, to squeeze into the tiniest blood capillaries ... but white blood cells have the same DNA as the rest of your body).

If your full sister inherited a mutation from a parent, then the same parent had a 50% chance of passing the same mutation to you. And 50% of not passing it, which is more practically important.

Sometimes, rarely, a mutation of a "cancer gene" is not inherited from the previous generation. Instead, something might have happened to the oocyte or sperm cells which merged to start the new life ... then a person might carry a new mutation, and pass it to the future generations, but the rest of the family isn't at risk. In a perfect world, a geneticist would always prefer to unravel the spool from the loose end. First test the highest risk family member. If something found, test parents. Move on to their children. Continue along the family tree, one branch at a time. The real world is a lot more messy and complicated, of course.

If there is no other cases of colon and endometrial cancer in your parents' families, I guess this gives the GCs a pause. Like, maybe there wasn't any HNPCC mutation there before. Maybe your sister is the first with some new mutation. But if that's what they think, then they should tell you to stop worrying about Lynch syndrome. They can't have it both ways. Either your sister got it from a parent (and then you can get it too). Or she didn't (and then you won't get her risk factor from your parents either).