Friday, June 18, 2010

Unaswered questions

I spoke a couple of weeks ago at a women's conference. During the question and answer period after my talk I was asked a question that might very well be the one of the most frequently asked questions whenever we speak. And it is certainly one that Dr. Gordon fields constantly.

"Could the test be wrong?"

Women who test positive often ask this question as they want reassurance that the tough choices that they face are really necessary.

But this was actually not the question I was asked. The woman who asked me if her test result could be wrong had tested negative. Yet she had several markers that increased her risk of being BRCA positive, including the fact that she has had breast cancer twice, once in each of her breasts. What she wanted to know was if the test could have wrongly identified her as negative. This test has little chance of being "wrong" because Myriad has stringent quality control standards. But this is not the end of the issue.

This story is a good reminder of the need for good genetic counseling, and for the need to follow up with your genetic counselor if your circumstances change. This woman, who for the purposes of this story I will call Ava, had seen a genetic counselor after her first breast cancer, which is when she tested negative. But she had not been back after her second breast cancer diagnosis. In the intervening years Myriad has developed the BRACanalysis Large Rearrangement Test, known as BART, which identifies mutations on the genes that are large rearrangements of sections of the DNA. These are mutations that are not identified by Myriad's standard test. This additional test might reveal a mutation that could not have been identified at the time of the earlier testing.

The other thing to remember is that the BRCA genes are not the cause of all breast cancer or even the cause of all hereditary breast cancer. Only about 10 percent of breast cancers can be attributed to the BRCA genes. And only about half of hereditary breast cancer is due to these two genes. We do not yet know the genetic cause of these other hereditary breast cancers. Research continues to seek new genetic links to breast cancer and someday soon we hope to know more. In the meantime, if you have tested negative for a BRCA mutation but have a strong family history of breast and/or ovarian cancer, stay in touch with your genetic counselor at least once a year to ask if there are any new developments that might be important for you.


  1. I've heard this question asked a lot too - have also heard the story of test results of two sisters getting switched. They tested on the same day, one was positive, one negative. They didn't find out until after the one who thought she was positive had a PBM. I'm not sure if this is one of those urban legends or not but the thought of that happening is pretty scary...

  2. There are a few issues here- first the question of getting the wrong test result. All labs have the potential to make an error, but diagnostic genetics labs are usually the most careful about sample handling. Myriad is fully automated, samples are bar coded (from the sender) and then handled by robotics once in the lab minimizing 'human error'. So if the story you relay above is true (I have never heard this, and it has never been posted or circulated through the cancer genetics professional groups, it would be due to the clinician drawing the blood and packing up the sample who switched the names. In my institution the genetic counselors only pack one specimen at a time and seal it before moving to the next patient. A patient can always ask to have the test repeated for their own assurance (particularly prior to making a decision to go forward with surgery) and I always insist on that if the testing was done via a research program.

    Next is the issue of the tests sensitivity, or ability to identify mutations. Like Joi discusses, the BRCA gene test has improved three times since clinical testing began, with major additions to the test in 2000 and late 2006. These newer molecular techniques identify mutations not seen by sequencing of the gene (reading the gene like a sentence). This is also true for the other known genes related to hereditary breast cancer (PTEN, P53 etc).

    Finally, sometimes the genetic test is just hard to believe. I have had several patients that have a known BRCA mutation in the family, have themselves had early breast or ovarian cancer, and tested negative. I have one 25 year old with breast cancer who's father carries a BRCA1 mutation who was tested THREE times (twice by her oncologist and then by me from her cheek cells) and was NEGATIVE. There is obviously something causing her breast cancer, but its not BRCA.