Help me figure this out...

K8orade_

Hi Ladies,

I need all the support and opinions I can get. I'm 30 and have never had cancer.
My family members have:
Paternal Gmother in 60-70s
Maternal Gmother in 60-70s
Mother at 49
All had in one breast and all survived. Gmothers died from heart problems in their 70-80s as far as I know.
Also my father was diagnosed at 61 with a carcinoid tumor in his large intestine.
When my mother had bc in 2008 she was tested for brca 1/2 and tested negative.

I recently saw my GC for my very first appointment and she said there have been many advances in genetic testing. Apparently there are new "places" on the brca genes that can be tested now? Along with a host of other genes now too, is that correct?

My mother has rejected testing so unfortunately we won't be able to get those answers from her. I will move along with my own testing now.
If I test positive for a mutation my risk will go up, if I test negative my risk will stay the same, right? Because I will be an informative negative?

Another question I have:
According to my pedigree and personal history, my GC has given me a risk percentage of 26.3%
My understanding is that 20% is considered high risk and qualifies me for increased surveillance. I've already been to a high risk consultation and set up my first mammo which will alternate with mri's every six months.
My question is this: how serious is this number, 26.3%? I understand I'm high risk but am I really just increased risk? What is the percentage range for that?
26.3 sounds horrible to me but it's also sort of on the fence. Not low enough for me to feel safe but not high enough for me to feel surgery would be best.

I'm confused because 26.3 is considered high enough risk for me to have increased surveillance. But it's also so low that (in my 30s) my chances of getting bc are sooooo low in the next 5-10 years.
To me that contradicts itself. I don't understand how my risk is double the average, 1 in 4 instead of 1 in 8, but also so incredibly low? I know it has to do with lifetime vs immediate risk but either way..I'm having a hard time making my husband see what a big deal this number is because he sees the yearly statistics and sees such a low risk probability. I hope all of this makes sense.

I also don't understand that if the probability of having a genetic mutation is so low, then why test? Isn't everyone's probability incredibly low? Or is my family history so significant that a mutation is expected? I couldn't get a clear answer from my GC because I felt like she had to offer testing just because it may be a liability if she didn't. I don't feel like I got her personal opinion of how serious this is or is not. She kept saying that testing is "appropriate in my case" but never led on about what she thought the chances of having a mutation were in her opinion. Does that make sense?
I'm just trying to get a feel for everything. Is this risk factor something that should make me think "oh wow. I'm probably going to get cancer but hopefully my mammos and MRIs will catch it early" or "I have imaging every six months so I don't have to worry about it"?
What would you think if it were you? If it were your daughter?

Thanks for letting me share my feelings and questions Hope to hear from you soon.

Ddw79

This territory is still a little uncharted . Are you meeting with a genetics counselor to go over these potential risks and numerical values. All we know here is what is considered " relative risk." Personal risk does not seem clear to me at all in this case.

I am at high risk due to surgical findings recently but even considering that all of the women in my family died of either breast or ovarian cancer this iny case is not a high risk factor for me. O was tested along with other family members in 1992 for the recently isolated BRCA1 Gene. It took almost two years to return my test results. Two other family members tested positive for BRCA1 in study. I brought them to Boston to be studied. I tested negative . This I believe would be a high confidence or informed negative. Yet I am one step before a breast cancer diagnosis. I do not believe that there is an obvious genetic etiology in my case. Breast Cancer happens. It sounds like you will be well monitored. In addition since you are so young and to date high confidence negative I would suggest that it would be well worth while to see a genetics counselor about other possible gene involvement and it's great in so many ways that you have living family membes to test too

leaf

I am definitely not a genetics counselor or physician. I totally agree with Ddw79: discuss your situation with your GC. I think an excellent question is not only what is your lifetime risk, but also how well do they know that number (in your case 26.3% I assume.)

I was diagnosed with classic LCIS about 10 years ago. When I saw an oncologist, he said my lifetime risk was about 30-40%. That's about what my genetics counselor said (~ 10 years ago.) I was told I have a BRCA risk about the same as an average Ashkenazi Jewish woman. My family history is somewhat better than yours: Postmenopausal (after the age of 50): paternal grandmother, several maternal aunts; post genetic counseling I have also had 1 postmenopausal cousin and one premenopausal cousin diagnosed with dc. I found one paper that described LCIS as 'high risk' and in another part of the same paper 'medium risk'. They still have not decided whether or not LCIS women should get MRI screening, even though of course 30% and 40% are more than 20%. (LCIS is an unusual condition.)

I have not had any further breast diagnoses worse than classic LCIS.

If the GC determines your risk of a BRCA mutation is relatively low, then do know that the science of breast cancer risk prediction is in its infancy. See this paper for comparing how well the modified Gail model did, which is not very good for individuals. The modified Gail model does really well for seeing how many women in a GROUP will get bc, but it does LOUSY for predicting whether ONE PARTICULAR woman (for example, you) will get bc. http://jnci.oxfordjournals.org/content/98/23/1673.... . (Lousy is my adjective - the modified Gail model is right about 60% of the time and wrong about 40% of the time for the general population. Notice that the toss of an honest coin would be 50% heads and 50% tails.) In the paper they say perhaps an exception may be for women with a single inherited mutation, such as BRCA.

vlnrph

Our original poster k8orade states that she has recently seen a genetics counselor and that her mother declines further testing. She is trying to sort out the practical implications of the information she has been given.

Ddw79, there are now several different mutations besides BRCA 1/2 which can be detected. Perhaps you should have an updated assessment given your dramatic family history. The prices and time to report panel results have come down a lot just in the past couple years.

Leaf, perhaps your premenopausal cousin or one of the affected aunts would be a good candidate to get the ball rolling to try and figure out what is going on. Once a defect is isolated, frequently the relatives only need to be checked for that particular variation which can make the cost quite affordable. Will you continue tamoxifen beyond 5 years? I agree with your analysis of the Gail model.

OP (cute name, makes me want to go drink something!) please realize that more data is being generated daily and that we will have better answers in the future. Right now, a set of baseline scans would be reasonable if your insurance helps cover the MRI. Make other decisions once you achieve a comfort level with the options available.

leaf

I have a quite large extended family. Since 1 in 8 women get breast cancer in their lifetimes on average, I don't think I'm that unusual. Even the sister of the premenopausal cousin wasn't recommended to have BRCA testing. The rest of the people are already deceased (from other causes.) The BRCA risk models I've found calculate my risk of having a BRCA mutation as about 2-3%.

My onc did not want to continue tamoxifen beyond 5 years, because I kept on having benign endometrial polyps.