Accuracy of genetic testing

sad-hubby

I had a thread about BRCA1 & Her2 but starting a new one since what I am looking for is somewhat different.

My wife who is 44+ was diagnosed with BC ER+ HER2+. She was treated neoadjuvantly - TCHP 6 rounds (once in 3 weeks) had lumpectomy with pathological report showing PCR. She was expected to go through radiation for 4 weeks to wrap up.

Now her Genetic testing result has come back. It shows that

pathogenic mutation or a variant that is likely pathogenic in the BRCA1 gene

She doesn't know of her immediate family members having breast / ovarian or prostrate cancer - at least not with her parents or aunts on father's or mother's side. At the same time her cancer was ER+ & Her2 which is somewhat uncommon.

This raises some doubts about accuracy of the testing. Few questions in this forum in case anybody faced similar situation

[1] Test was done by Ambry Genetics in Vallejo CA. Anybody with experience with that company?

[2] Does the result show specific mutation? We are part of Kaiser so that what we got one line statement (please see above) with some explanation about what high risk means but no mention of specific mutation(s).

[3] Anybody diagnosed with BRCA1 positive had Her2+ ER+ BC?

We would like to understand the result before taking drastic decision like double mastectomy. Any information will be appreciated.

inks

My genetic test was done by Myriad and it stated the specific mutation. I am sure yours did too. Did you see a genetic counselor? They should have the full report and the mutation.

Your wife is over 40 and the prevalence of ER+ in BRCA1 mutation carriers raises with age.

If your wife's family is small, people passed away at a young age from other diseases there may not be very obvious clues about BRCA. If you saw the genetic counselor they probably made a suggestion to test other family members and most likely the first one to test would be your father in law. BRCA can travel through male line almost undetected. Your genetic counselor could have explained you all that, I would ask my co-pay back since they did a crappy job.

I think you will have less doubts about the accuracy of the results once another family member tests positive for the same mutation. Their testing would also be less expensive since they would only be testing for one mutation and the insurance company is more likely to approve it since somebody already tested positive.

besa

I had genetic testing done at Ambry and I am guessing there is MUCH more to your report than what you were given. I had "Breastnext" testing done by Ambry a few months ago and came up with a variant of unknown significance in one of the genes in the panel (not a BRCA vus). Ambry gave me a ton of information -- the exact DNA base change and location, a chart showing the sequencing of the same gene in many different species. (This is done because variants that tend to be unimportant (harmless) often to show up in the sequence of other species -- very important sequences tend to be conserved across different species and if there is a change in a very conserved sequence it is more likely to be harmful.) They also gave me the names of university research labs (and contact information) studying the gene in question (done so I had the option of putting myself in a study) and additional information concerning the gene in question.

You wife should ask for the actual report that Ambry sent to Kaiser. She is entitled to it. It is part of her medical records. (The HIPAA laws entitles your wife to a copy of her medical records.) Once you have the exact BRCA mutation, and if you are still concerned about the accuracy of the test results, you could ask to have a blood or saliva sample sent to another lab. Sequencing is expensive but retesting for an exact mutation costs much less - it is something you might decide to do even if insurance doesn't cover it.

(As an aside the genetic counselor I saw told me she considered Ambry a lab that did quality work.)

A great source of information and support for women dealing with genetic issues and breast cancer is FORCE.

www.facingourrisk.org

It is possible to be high risk and have a BRCA mutation without having a huge family history of breast cancer or even any family history that you know of. The information of a cancer diagnosis could be hidden by other older family members. As inks said the mutation can also be passed for generations from father to son. Family members could have just been lucky and though high risk just didn't end up with bc. Also there are other cancers that are associated with BRCA mutations (see the FORCE web site) so even though there may not be breast cancer, prostate or ovarian cancer in the family there could be other cancers indicating a BRCA mutation. Has your wife seen a genetic counselor? A genetic counselor should be able to give you more information and help you figure this out.

farmerlucy

Color Genomics recently released a multi gene breast and ovarian cancer panel. It is $249 self pay only. It looks at 19 genes including the brac. I don't know anything about it's reliability except to say it is backed by some very heavy hitters. I did it last week. A bonus for me is a retest of the brac