Hi BlueSky,

From the main Breastcancer.org site's page on What to Do if Your Genetic Test Results Are Uncertain:

"If your test and your family members’ test results are negative, but many young women in your family (younger than age 50) have been affected by breast and/or ovarian cancer, the cancer in your family could be due to an inherited genetic abnormality that has not yet been identified. The same holds true if your results were negative but you were unable to have a family member with cancer tested. In these cases, you still could be high-risk due to another genetic abnormality besides BRCA."

For information on what steps you and other family members can take in this case, read more here.

We hope this helps!

--The Mods

There is a difference between an uninformed negative, and a true negative.

A true negative only can happen if there is an identifiable mutation in your family. Those who are affected by cancer carry a known deletrious/harmful mutation. If you for example were then negative for that mutation, you are more than likely to be at average risk. You are a true negative. This does not mean you are immune from a sporadic cancer, but that your cancer will not be a result of the genetic mutation in your family. There are families where a true negative person does still develop cancer. Remember that about 12% of women in North America will develop breast cancer, and around 90% of breast cancer IS sporadic (meaning no family hx of breast cancer) so sporadic cases can still exist in families with a mutation.

An uninformed negative is either someone who has tested negative but has no way of knowing if there is a mutation in their family (no one who has been affected is willing to or iis alive to test) or is someone who comes from a family where affected family members have tested negative. It is known that BRCA 1 and 2 do not explain ALL hereditary breast and ovarian cancer, but they do explain about 90% of it. The other 10ish% is still an "unknown". It may be other BRCA1 or 2 mutations that have not yet been discovered. It may be mutations in CHEK2, STK11, and so on....or it may be a result of polygenic factors (many variants or unknown mutations working together). Being one of these people does NOT mean that your risk can be assumed to be "average", and your risk will be assessed based on your family history and personal factors.

I am an uninformed negative in a family with a very strong cancer history, and my risk assessments have been around 40% (I have had 2 or 3 of them now) making me high risk according to clinical guidelines. This risk assessment is based on family history, personal history, breast cancer risk models, and various studies out there. Of course, this risk assessment is given to me by genetics experts, not my own self-assessment. One study by Dr. Narod for example (a Canadian study), that my Canadian genetic experts relied on, found that women in BRCA-negative families with 2 close relatives with dx under 50, or 3 close relatives of any age, had about a 40% risk.

So, a genetic test is very telling in a couple different scenarios:

1. You have affected relatives with a known harmful mutation; you test either negative to be a true negative, or positive to know you carry the mutation that causes cancer in your family (and most likely other families).

2. You do not have affected relatives available to test; you test positive for a mutation KNOWN through testing of other families to increase risk (meaning you do not show up with a variant of uncertain significance, etc). For example, no one in your family may have tested, but you do test positive for BRCA1 185delAG, which is one of the three main founder mutations.

If you do not have affected relatives who have tested/can test and you test negative, the results will not be informative. Similarly, if your affected relatives HAVE tested negative, there is no point in you really testing (but see my disclaimer at end of this paragraph). Whatever is causing the hereditary cancer in your family is not yet known. Important disclaimer: it should be noted research is ALWAYS going on and new mutations are being discovered (in BRCA and in other genes) so it is important to know WHAT exactly your relatives tested for, and discuss whether new testing would be beneficial for them or you with a genetics expert based on new advances in research/testing.

Ultimately, you kind of need to decide whether genetic testing is a benefit to you and whether or not it will affect your own decision making or care guidelines and what you would do if either a positive OR negative result, and how such results could be interpreted. It is really best to talk to a genetic counselor as you make these decisions, including about whether or not testing is a benefit to you or something you wish to do, and what testing is appropriate.

BlueSky5...those who test negative for that mutation would be a TRUE NEGATIVE (another disclaimer: an exception may be if you were from an Ashkenazi family, where one was only tested against one known founder mutation that had been identified in the family. These families are more likely to have more than one mutation in the family bloodline from the 3 founder mutations, which is why reflex testing for the three mutations is usually offered).

There is a very good amount of research to show that those who are true negatives really are NOT at increased risk at all, unlike their BRCA+ relatives. They are at average risk. They may still develop sporadic cancer, but the guidelines are to screen them and so forth according to the "average" guidelines for the general population....not as high risk. I don't know any genetic counselor that would say a true negative remains at increased risk, this would run contrary to what the research has indicated.

Negative BRCA testing may not always imply lowered breast cancer risk

http://medicalxpress.com/news/2013-11-negative-brca-imply-lowered-breast.html

There is no genetic issue matters in the case of cancer. It can happen to anyone. Family history does not matters a lot, as i can say. If a person of a family is diagnosed with the cancer that does not mean all the generation from the person will be diagnosed of cancer. It is not complicated if diagnosed negative.