Genetic testing- can you have a false negative result?

blue22 is right. A negative result means negative for what was looked at. But what is looked at are only those genetic mutations that are known at the time to increase risk. New variants of genetic mutations are discovered regularly.

It's not uncommon for those who have full genetic testing to get a VUS result, which means that they were found to have a variant of unknown significance. In other words, there is an abnormal mutation in the gene, but it's not yet known if this particular abnormality is tied to increased risk or not. Over time, as more people are found to have this same VUS, it can be determined whether or not this variant does increase risk. If it does, at that point the variant will be added to the list of what is looked at when doing BRCA testing.

This is why a negative result today might not be a negative result next year, as new variants are added to the list. When I had BRCA testing, after getting my negative result, my genetic counsellor suggested that I could come back in a few years to be tested again, because she knew that by then there would be many more variants that would checked.

It's also true that some testing facilities only look at a small subset of even the currently known mutations. 23andMe only check for the 3 most common BRCA mutations. There are more than 1000 other less common BRCA mutations. It's possible that some labs might also not check all the known mutations.

With genetic testing, the only "true negative" is when there is a known genetic mutation in one's family - a very specific variant of the BRCA1 gene, for example - and someone is tested to see if they have this family genetic mutation. If they test negative for that specific mutation, then it is called a true negative. For the rest of us, a negative result is an "uninformative negative", which means that nothing was found in what they looked at but there could be a mutation or variant that we have that was not checked for or that is as yet undiscovered.

My genetic testing shows no mutations for any cancer yet I have two. All I can say is my cells decided to mutate (or as my husband says, I'm an overachiever). Sometimes there's not a clear reason.

beesie is a treasure!

Jon's girl, yup, there are still no answers to many of the questions we have about bc. But I can tell you that I have seen progress in the 8 years since I was dx'ed. The only genetic testing that was done 8 years ago, for me, was BRCA testing, but now they can test for over 30 gene mutations. I had the Ambry panel last summer (still all negative).

Myriad is a reputable company. I may be wrong, but I think doctor ordered testing is done through companies that are available to the medical profession as opposed to ancestry or 23 and me, which is consumer targeted. I don't think medical professionals use those companies, but I could be wrong

VLNRPH's point re: having insurance in place prior to testing cannot be stressed strongly enough. The same concerns apply to any offspring that might be considering testing. Once the cat's out of the bag, it isn't going back in.

If you're going to be tested it's important to use a highly reputable company that specializes in this kind of genetic testing AND is bound by HIPAA. Companies such as 23andMe, for example, test for ONLY the 3 most common BRCA mutations, as Beesie pointed out. They are also not bound by HIPAA. In my opinion, why waste your money on that and expose your genetic information to possible commercialization or other risky uses?

If your MD or whoever won't order testing, Color Genomics is the one company that I would trust. They do provide genetic counseling and they are bound by HIPAA. Their rate is very reasonable - I think it's $250, with reduced rates for family members if you are found to have a mutation.I

As to which genes they are looking for - there are specific panels that may be recommended by a genetic counselor based on your family history. There are panels for breast cancer mutations, colon cancer, prostate cancer, etc.

Regarding re-testing - I was told by Myriad that they will notify my genetic counselor, or any other medical professional I designate, of any changes that affect my report. In addition, it's fine to call back after a few years to see if there are any updates. Whether those who had a negative result would need to re-submit saliva or blood I do not know.

Genetic testing can provide a wealth of extremely useful information but it's vital to understand the ramifications beforehand.

Jons_girl, My maternal grandmother had uterine cancer, my paternal aunt had breast cancer, my mother had breast cancer, my father had kidney cancer. I've had endometrial/uterine, breast, and kidney cancers. Plus Dad and I both had several skin cancers, but just the basal cell type. The genetic test I took in January showed no connection with any of these. My insurance limited how many things were tested, and I only did the testing because my BS recommended it. I don't particularly want to know if I'm prone to get another type of cancer, and have anticipatory worry over something I can't control in the first place. "Shit happens" is good enough for me.

There was no cancer in my family that I know of, but my BS suggested genetic testing using a genetic counselor. The insurance would only cover BRCA testing so I paid more to get more extensive testing; I think they were checking about 43 gene mutations. I am not sure what I will feel if some of these come back positive or if there is anything that I can do proactively to avoid cancer. But I felt that even if there is currently nothing to be done to prevent certain types of cancer, there could be in the future so that knowing that I had a gene connected to cancer was better than not knowing.

Here is the link to Ambry's website:

https://www.ambrygen.com/patient

I want to add that I had extensive genetic counseling prior to my original BRCA testing years ago. This included having to take an online “class" which explained every aspect of gene testing and possible implications in real life . There was even a quiz at the end! When I met with the genetic last summer prior to the more extensive testing, she was able to answer all of my questions and address any concerns. BTW, my all inclusive HMO requires that anyone they recommend for genetic counseling take the online class and meet with a genetic counselor. They really want people to understand what gene testing can and cannot reveal as well as how it may effect other aspects of your life.

Because of my ethnic background testing was recommended. I have daughters and granddaughters so although I already had bc, my family and I needed to know how their health might be effected

Jons girl - Hope you got the all clear at your check up today and are set to enjoy the weekend.

My HMO would not pay for genetic testing.

So, I paid $250 for the Color Genomics testing for hereditary cancer, hereditary cardiac, and response to medications.

This kind of testing shows the mutations you were born with—what your mom and your dad gave you at birth. It does not measure the mutations that happen over your lifetime due to aging, environment, etc.

The good news is that I had NO HEREDITARY CANCER MUTATIONS!

The bad news is that I have two simultaneous primary cancers, papillary thyroid cancer and metastatic breast cancer found in 3 central neck lymph nodes (with no primary breast cancer identified despite extensive diagnostic testing, including PET scan, MRI guided breast biopsy, breast sonograms, and 12 years of annual mammograms).

Still, it is comforting to know that I probably have not passed along any hereditary cancer or cardiac mutations to my adult children, so for me the testing was worth it.