Tag Archives: Mutation

BRCA mutations and me

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BRCAaskmeAfter a couple of recent messages from readers, I realized that I don’t talk about my genetic status much … you have to do some digging to figure that out. Well, I’ve updated my About page and here I am clarifying: I am a BRCA uninformed negative. If you’re already confused, scroll down for an explanation of BRCA and its significance in the cancer world.

What is an uninformed negative?

There is a distinction between a positive genetic test result and a negative one, obviously, but there is a further separation between true negative and uninformed negative. The former diagnosis is made when a mutation has already been identified in the family line, but the person tested does not carry that mutation. The latter applies to individuals like me, whose family tree DNA does not present any known mutations associated with the increased occurrences of cancer. It is still a mystery and we remain uninformed.

Aside from the most commonly tested BRCA1 and BRCA2 genes, there are many others that impact risk of breast and ovarian cancer, such as PTEN, CHEK2, ATM, TP53. The clinical significance of mutations on those genes varies from that of BRCA mutations, however. My genetic counselor and I are discussing testing for these. I am aware that it is possible my sister and mother, who both died from gynecologic cancers, carried some gene mutation their limited testing did not uncover and I did not inherit it, so we are considering importing my mother’s blood sample from Europe to be thoroughly tested in the US. To find out how to assess your risk, learn more about counseling, or find a certified counselor, visit FORCE.

Also, if you are a fellow uninformed negative, there’s a Facebook group for that! Join us.

Now, for the nuts and bolts of this …

What is BRCA?

Everyone has four BRCA (BReast CAncer) genes: one copy of BRCA1 inherited from mom, one from dad and same of BRCA2. They produce tumor suppressor proteins, which help repair damaged DNA. Mutations present in these genes result in production of defective proteins unable to do their job, which can result in genetic alterations and ultimately lead to cancer.

Together, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers. In addition, mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall. Breast cancers associated with BRCA1 and BRCA2 mutations tend to develop at younger ages than sporadic breast cancers. – National Cancer Insitute

An important thing to note: as long as an individual has one properly functioning gene, they are producing those DNA-repairing proteins and remain protected. Not until the second copy of the gene is mutated does their chance of developing cancer skyrocket. Somatic mutations can occur due to exposure to carcinogens, such as certain chemicals found in prepared foods (I’m looking at you, hot dog), cigarette smoke, asbestos, radiation, alcohol, etc. Eat healthy, live clean, wear sunblock, lay off the booze!

This is a really great video shared by Andrea on her blog Brave Bosom. It explains mutations, how they relate to cancer, and how treatment affects cells.

Genetic testing can determine whether an individual is a carrier of a known BRCA mutation. There are well over three thousand BRCA mutations that have been identified, however not all of them are clinically significant, which means they either don’t increase risk of these cancers or we don’t yet have enough data to comfortably say so. Here is the break down according to another blogger’s analysis of data available from the National Human Genome Research Institute’s Breast Cancer Information Core database (say that three times fast!). Although this database contains a wealth of data, this analysis is from a specific point in time. New mutations are discovered every day! If you’re a data nerd, hop over to Jessica’s blog to read the full post and her story: Breaking BRCA.

BRCA mutation counts

*Please note that I am not a genetic counselor or a healthcare professional and am only presenting my experience and what I leaned from doing my own research. Please consult a doctor or certified genetic counselor if you have questions or concerns about your own genetic status and associated health.

Previous posts on the topic:

Genetic testing for BRCA mutations

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BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumor suppressors. Mutation of these genes has been linked to hereditary breast and ovarian cancer. – National Cancer Insitute

A woman’s risk of developing breast and/or ovarian cancer is greatly increased if she inherits a deleterious (harmful) BRCA1 or BRCA2 mutation. – National Cancer Insitute

Having a BRCA gene mutation is uncommon. Inherited BRCA gene mutations are responsible for about 5 percent of breast cancers and about 10 to 15 percent of ovarian cancers. – Mayo Clynic

My mom, who was diagnosed with ovarian cancer in June ’12, just got the results of her genetic tests. The news is good, in that there were no mutations detected, however the test looked for only three mutations/variants on the BRCA1 gene (300T/G, 4153delA, and 5382insC). Only three out of hundreds of different types of mutations that have been identified! And the test only checked the BRCA1 gene. I’m inclined to chalk this up to the fact that she’s in Europe and maybe genetic testing isn’t as common practice there as it is in the US, but nonetheless I am dumbfounded. She has submitted another blood sample with a request to run a more thorough analysis.

This made me take a closer look at my own negative BRACAnalysis test results. The tests done were: BRCA1 sequencing (5-site rearrangement panel) and BRCA2 sequencing. The narrative explains: “there are other, uncommon genetic abnormalities in BRCA1 and BRCA2 that this test will not detect. This result, however, rules out the majority of abnormalities believed to be responsible for hereditary susceptibility to breast and ovarian cancer.”

So … what now? As far as further testing (BRACAnalysis Rearrangement Test – BART), I’m not sure that it is necessary. Per Myriad: “there is, on average, a less than 1% chance that BART will identify a mutation in a patient who has already had a negative result from Comprehensive BRACAnalysis.” I’m going to wait and see what my mom’s results are. In any case, this doesn’t change my decision to move forward with the prophylactic bilateral mastectomy in January, but creeps back another variable thought to have already been checked off the list.

Side note: In this blog, I’m only addressing my choice to have a prophylactic bilateral mastectomy to reduce my risk of breast cancer. I am conscious of our family’s history with ovarian cancer. That is another topic for another day. At this time, I have decided to keep a close eye and wait until I hit menopause to seriously consider an oophorectomy.

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Update 10/16: Mom’s second genetic test results, which also checked for PTEN mutations, were negative. I gave blood for BART anyway and my results were also negative.