O.k. I am confused now about results

This is just a mini-Biochem overview. 

I have not been genetically tested, but I was genetically counseled.  I opted not to be tested because my family history is weak.

This is what I understand of the BRCA situation (a little simplified).  Everyone has the 2 BRCA genes, BRCA 1 and BRCA 2.  Genes are made up of DNA. DNA is made up of many different nucleotides, which code for different amino acids.  (3 consecutive nucleotides code for one amino acid.) Protein is made up of many different amino acids. (There are at least 12 naturally occuring amino acids - I think there are a lot more than this.)(They can also have many complex sugars attached, and other proteins associated with them, etc.)

If your DNA get mutated, or if you inherit a mutated gene from your mother or father, it has a different nucleotide in it.  This means it is different from the 'average'  BRCA1 or BRCA 2 gene.  Mutations can occur at hundreds/thousands/millions/billions/zillions of different places, and at each position can make a thousand/million/zillion different changes at EACH position.  Each mutation can be for a different amino acid, or group of amino acids in the protein. So you can have zillions of different mutations.

From your mother you inherit 1 (BRCA1) gene and 1 (BRCA 2) gene.  From your father you inherit 1 (BRCA1) gene and 1 (BRCA 2) gene.  For most people, the BRCA 1 and BRCA 2 genes are what most people have - 'normal' or 'wild type'. We don't know precisely what the BRCA genes do, but they probably have something to do with repairing DNA mutations (I think-I have not looked this up.)

*Everyone* has some mutations in their genes. If you are BRCA 1 and/or 2 positive.  There is no person who has 100% 'average', 'wild type' genes. So we are all 'mutants'.

In some families, the BRCA1 or BRCA2 genes can be different from the 'normal' or 'wild type'.If you have a mutation (difference), this can be called a variance.

So there can be zillions of different mutations in the BRCA 1 or BRCA 2 genes. 

Now, a mutation (change in the DNA), may lead to no change in function at all. 

One of the basic principles of protein structure is that protein structure (shape, where there are positive and negative ions, etc.) can affect protein function.

Proteins are often big huge molecules.  Some proteins are enzymes, which means they help a reaction go faster (or slower). Most enzymes are VERY picky what reactions they will do.  These reactions happen at very specific parts of the protein molecule.  At other parts of the protein, it won't make a difference.  So you can have one mutated enzyme that won't work at all, and another one that works fine, because the mutation was at an inconsequential place.

So you can have a mutation that is 'significant' - it changes a place in the portion of the protein that makes reactions go, or you can have a mutation in a place that is insignificant - where it doesn't matter.  

We often don't detect when we have an insignificant mutation, because it doesn't change the function of the enzyme.  (A change in the structure of the enzyme can change the function of the enzyme.  Also, for other proteins that are not enzymes, a change in the structure of the protein can change the function of the protein.)

So you can have a mutation of significance - where the BRCA 1 or 2 genes is mutated.  So, for a hypothetical example, at amino acid position 493 there is one amino acid called alanine instead of  the amino acid tyrosine.   (Its been too long so I don't know if they name the mutation in terms of the position of the amino acid, or the position of the nucleotide. )

So you might have a mutation called '493 ala' ( ala is short for alanine).  That means (I think) you have alanine at that position instead of, say, a tyrosine (tyr).

Now that mutation may or may not be 'significant'.  There are some mutations that we know are associated with a high rate of breast cancer and ovarian cancer.  Those people have a known mutation.

Other people might have another mutation, say at (hypothetically) position 2857, the 2857th position in the molecule, that has been changed from the amino acid leucine (leu) to isoleucine (I can't remember the abbreviation for isoleucine.) (These are names of amino acids).  Maybe we don't know of any families with this particular mutation.  Or maybe we can't tell whether this mutation causes problems.  So this might be a varience of 'unknown significance.'

There are many different types of mutations.  For example, you can have a nucleotide missing, which messes up not only that amino acid, but also all the following readings of amino acids.

When you find what your variant is, one place you may want to search out is the FORCE website (if you haven't already).   http://www.facingourrisk.org/

I know this is long winded, but I hope it gives you a mini-Biochemistry 101 overview.

Oh yes, you understand!  (I sometimes say I speak Martian because I often don't communicate well.)  They probably don't have enough information to know if your mutation will cause more breast cancer or not.  Since there are zillions of different possible mutations in a gene, a lot of mutations may fall into this category.  (I am speaking in general here; I don't know specifically about BRCA.  I am NOT a genetics counselor.) For some genes, a mutation in a certain place may not only cause disease, it may cause death of the cell.  For example, if the gene coded for an enzyme that was necessary for the cell to get energy, and there was no other  alternative gene or pathway, that would cause the cell to die.  So, if this happened prenatally, the cell or fetus would die/miscarriage.

The VAST VAST majority of the known single gene inherited breast cancer mutations are in the BRCA 1 or 2 genes.  The genetics counselor said I might have a PTEN mutation, but needed to check with her advisors.  I later found that there have only been about 300 people, worldwide, ever, that have been diagnosed with a PTEN mutation.  (However,  its undoubtedly under diagnosed.) They said it would 'not be medically necessary' for me to be tested for PTEN. There were only, say, 6 different boxes (about 6 different genes) for the MD to check off on my  preprinted genetics referral in 2006.  

There are undoubtedly undiscovered breast cancer gene(s).  We can't say a whole lot about them because we don't know much about them.  So there are families where almost every single female gets breast cancer, yet they test negative for BRCA1 or 2.

I was tested for the P53 gene and they found a variant that was not suspected in my cancer.  But I was told to call once a year to check on the info as it is an area that is rapidly changing.

These are the Prevtive Task Force guidelines for BRCA testing.  They may not be very accurate if you have some unusual patterns in your family tree, such as all sons in a generation, or only a single  offspring in a generation.

"These recommendations apply to women who have not received a diagnosis of breast or ovarian cancer. They do not apply to women with a family history of breast or ovarian cancer that includes a relative with a known deleterious mutation in BRCA1 or BRCA2 genes; these women should be referred for genetic counseling. These recommendations do not apply to men.

Although there currently are no standardized referral criteria, women with an increased-risk family history should be considered for genetic counseling to further evaluate their potential risks.

Certain specific family history patterns are associated with an increased risk for deleterious mutations in the BRCA1 or BRCA2 gene. Both maternal and paternal family histories are important. For non-Ashkenazi Jewish women, these patterns include 2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger; a combination of 3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis; a combination of both breast and ovarian cancer among first- and second-degree relatives; a first-degree relative with bilateral breast cancer; a combination of 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis; a first- or second-degree relative with both breast and ovarian cancer at any age; and a history of breast cancer in a male relative.

For women of Ashkenazi Jewish heritage, an increased-risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer.

About 2 percent of adult women in the general population have an increased-risk family history as defined here. Women with none of these family history patterns have a low probability of having a deleterious mutation in BRCA1 or BRCA2 genes."

Elora, with the hereditary cancers, the majority is BRCA1/BRCA2. But it is often impossible to tell with confidence if the cancer is truly hereditary in a family (rather than several unfortunate but random events). It takes a real large family, and lots of ca cases, to be absiolutely sure. Otherwise, the geneticists would say that it is "familiar" but stop short of saying "definitely hereditary". And for families with regular-strength cancer history, suspicious but not extraordinary, sometimes no more than one patient out of 10 tests positive! Most of the rest of them aren't high-risk genetic.

 Some Uncertain Variants are contributing to cancer risk (although the majority of them are benign, just not yet proved to be fully benign). It is a huge burden of proof for a lab to declare a variant hazardous, so for a while, the indications of danger may be growing stronger and stronger, but the variant still remains oficially "uncertain". If you are OK with handling your own Variant with the help of still-incomplete data, then do some research about the particular variant you have. Google is a good to place to start. Myriad has some info to share. And of course there is an active discussion of various variants at the forums of facingourrisk.org !

Runalot, same advice to you. Find out which variant is yours, and start looking for clues about it. There are some "uncertain" Variants with zero info about them, but most of them have some helpful studies already.

Thanks for the update, Runalot!

You know, since this BRCA2 A75P has been reclassified as benign, it's no wonder that you couldn't find it on FORCE boards. It simply doesn't bother anymore anyone who's been tested more recently. B9 is b9, no reasons to worry. And everybody who had this variant reported in the earlier years, when it was still "uncertain", has been sent a letter explaining that it's no longer uncertain & no reason to worry.

But the catch is, there is no guarantee that the letters reached every patient. Doctors could have moved or stopped practice, patients could have moved or changed doctors... With your own base-to-base relocations, it's almost a given that the new info may never reach you. Lost in the chain of moves. Well, you tracked it now. Maybe we should all congratulate you with your newly negative BRCA result!

In truth, it's great news but it isn't perfect. Between your biopsies and history of early breast cancer on both mother's and father's sides of the family, one negative result comes short of an absolute victory over the fears of genetic risk. Because there are some rare mutations which today's tests do not detect. Very uncommon mutations but they exist, and until there is better clarity about the mutation status of your relatives, some fears may still linger. If your mother, or your father's sister with ca, would get tested & a mutation is found there, then your level of certainty increases. Because you'd know that there wasn't any "invisible" or "undetectable" genetic mutation. You'd know that there was a "plain vanilla" mutation in your family, and you haven't got it, clear and simple.

Good luck with your healing in time to train for December! Yes, I thought I run "a lot" but this year I met gals who run 100-milers and it just blows my mind....

FORCE? As always, the best parts are in the forums! Like this 20-page (really) thread about different mutations

http://www.facingourrisk.org/messageboard/viewtopic.php?t=15552

Not that it's still important for you now that you are officially negative! But there is a lot more chatter and discussion there, probably hundred fold the traffic of this forum here. Yeah - the companionship of the running people is amazing, I mean not everybody's is nice but ... almost everybody.