Second Opinion
My genetic test came back positive for a BRCA2 mutation. There is NO history of breast or ovarian cancer anywhere in my family so my mom feels like I should get a second opinion.
Has anyone gotten a second genetic test? How likely are these to be wrong in the first place?
Thanks
Comments
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Just because there isn't history of cancer in the family doesn't mean that you aren't BRCA2+. Your own cells can mutate! My sister has neurofibromatosis Type 1, a genetic disorder that she has passed on to her son. However, both of my parents have tested negative for the gene that causes NFB Type 1. So, my sister's cells mutated despite her lack of gene inheritance.
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My understanding is that BRCA1 and BRCA2 are germline mutations, and aretherefore always inherited from a parent.
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jspringer - there is a slim possibility that your BRCA2+ is a de novo germline variant, meaning that your parents passed on the genetic material but the germline mutation occurred at conception, meaning that they would test negative by a blood sample because the only BRCA2+ material is egg or sperm, not other cells. More likely though is that they did pass the BRCA2+ to you but nobody in the recent generations has developed cancer from their genetic mutation. The development of assorted types of cancer from BRCA2+ mean there is elevated risk, but it is not 100% guaranteed.
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I second what SpecialK wrote. As for a second opinion, do you mean submitting a new sample for genetic testing or simply having another doc review current test results? I am not sure that insurance would cover a repeat of the test but more importantly having the mutation does not mean you will be guaranteed to develop bc. So as was explained you can have family members who are carriers but have never developed bc. Take care.
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I have DCIS in my left breast and potentially invasive LCIS in my right breast (they cancelled my ultrasound when I came back BRCA2+), and I’m 45, so that’s why I was tested even though I have no family history. My surgeon wants to now do a double mastectomy and also remove my ovaries and Fallopian tubes.
My mom is concerned, and I think rightfully so, that I will have significant irreversible surgeries because of this test result and there could be a chance it’s wrong.
My care coordinator is checking to see if it’s even possible to have my sample checked by another lab. I was just wondering if anyone had any experience with this.
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"Some individuals who have inherited a germline BRCA1 or BRCA2 mutation never develop cancer because they never get the second mutation necessary to knock out the function of the gene and start the process of tumor formation. This can make the cancer appear to skip generations in a family, when, in reality, the mutation is present. Persons with a mutation, regardless of whether they develop cancer, however, have a 50/50 chance to pass the mutation on to the next generation.
It is also important to remember that the BRCA1 and BRCA2 genes are not located on the sex chromosomes. Therefore, mutations can be inherited from the mother or the father's side of the family." https://stanfordhealthcare.org/medical-conditions/...
I don't think it's likely to be wrong. I think it's just likely that your family has been lucky. Tumor formation is dependent on many things - not just a mutation but exposure to various substances and stressors.
The other possibility is of course a question of paternity. Genetic testing has been unveiling that a lot of people had different fathers than they thought https://www.theguardian.com/lifeandstyle/2018/sep/...
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TBH, I have not heard of any errors or problems with genetic testing in my 10 years on bco. That doesn’t mean it can’t happen I suppose but it seems unlikely. Family history of breast cancer is the exception not the rule. The majority of those who develop bc do not have any genetic mutations. Take care.
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One less expensive way of testing BRCA again is to submit a saliva sample to 23andMe. I was BRCA tested at diagnosis because I am adopted with zero information about family history. My BS was not going to make a recommendation regarding surgery type without that info, so I did the blood test. I was negative and we proceeded with surgery, but years later I sent a sample to 23andMe to try to get more info about my adoption and find blood relatives. As part of their suite of testing they included BRCA and some additional tests, which confirmed my earlier result. I believe you can get this done for about $200, but there is also Color Genomics for about $250 for a panel of genetic tests, including BRCA, which allows a similar type of online ordering without running the testing through insurance or bearing the full cost of re-doing your testing with a lab selected by your own doctor.
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I would caution against relying on 23andme. They only test for 3 specific mutations. I did 23andme a couple of years ago, and I was negative for BRCA1. As you can see in my signature, I do have a harmful BRCA1 mutation.
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I have a similar situation in that going back generations on both sides there is no evidence (or at least no evidence in current memory) of breast/ovarian/prostate cancer and so the BRCA test seemed like overkill until it was returned BRCA1+. I did briefly think that it could be wrong, but the sensitivity of the testing has to be so high that it is unlikely it would be a false positive. My mother has since tested negative and we are awaiting my father's test results, although logically it must have come down that side of the family (unless is a super rare de novo genetic mutation case which I doubt).
The genetic counselor in the US my parents saw warned the same thing about the commercial panels, and pointed this out especially due to the relative rarity of BRCA1 and it would likely not have been picked up on those.
jspringer - I would rejoice that you have this knowledge now, especially as you found out with "only" a DCIS diagnosis. Technically you do have options and could possibly elect for ongoing monitoring rather than multiple surgeries. That being said, I was more than happy to get my ovaries out a few months ago for various reasons and wouldnt necessarily dismiss that surgery out of hand - ovarian cancer is more difficult to catch early, especially if you don't have regular scanning.
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I became curious about the spontaneous appearance of BRCA genes so dug around a bit. Yes, the mutation can arise spontaneously
https://columbiasurgery.org/breast/brca1-and-brca2-genes-and-breast-cancer-survival
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Jspringer, you said you saw no breast or ovarian cancer in the family tree. According to cancer.gov, BRCA mutations also confer an increased risk of Fallopian tube, primary peritoneal, prostate, and pancreatic cancer. Are there any of these on either side?
I think I understand your desire to feel certain there is no mistake before choosing risk-reducing surgery. Here is an idea: Instead of re-doing your genetic test, have your parents test for the particular BRCA mutation that was found for you. That would be confirmation of an inherited mutation. Since they have a first-degree relative with the mutation (you), single-gene testing for them is within guidelines and should be covered by their health insurance. It would also clue the parent with the mutation that they could get extra screening for themselves.
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In addition to everything already said, it's important to understand that not all BRCA mutations confer the same risk. Some mutations are extremely high risk while other mutations are lower risk, although all confer a higher than average risk.
BRCA Gene Mutations: Cancer Risk and Genetic Testing https://www.cancer.gov/about-cancer/causes-prevent...
"By contrast, 55%–72% of women who inherit a harmful BRCA1 variant and 45%–69% of women who inherit a harmful BRCA2 variant will develop breast cancer by 70–80 years of age. The risk for any one woman depends on a number of factors, some of which have not been fully characterized...
...39%–44% of women who inherit a harmful BRCA1 variant and 11%–17% of women who inherit a harmful BRCA2 variant will develop ovarian cancer by 70–80 years of age. "
The specific BRCA2 mutation you have might put you and your family members who also have this mutation at the lower end of the risk scale for being BRCA positive. If the risk of breast cancer is 45% and the risk of ovarian cancer is 11%, it's very possible that the mutation is in the family but no one developed these cancers until you.
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aram - agree - I would not rely on 23andMe as the primary source for testing either. For me it was confirmatory. If it returned a negative result for the OP a more extensive look would be necessary. I’m sorry that you had a negative result followed later by a positive one, that had to be an unwelcome surprise.
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