BRCA negative but high risk. best risk assessment model?

Models are not a definitive answer. I agree with Melissa that a specialist might be a good resource for you. Genetic counselors with a master's degree can be found in community hospitals but you may need to go to an academic medical center in order to find a fellowship trained MD.

Usually, an individual in the family who has already had a cancer is the best candidate for testing. Panels available from Ambry, for instance, cover several potential mutations. Myriad had a monopoly on BRCA for years and is not my personal choice for that reason. Prices have come down in the past 18 months since their patents were set aside and insurance companies are more likely to approve coverage. Once a particular defect is identified in a family, sometimes other research labs can look just for that (single site analysis) at a very low cost.

I have a very similar family history and I am also negative for BRCA. I've seen breast cancer surgeons and genetics counselors and frankly, the level of guidance for people like us is abysmal.

The article Leaf referenced is an excellent one. It is hard to make clinical management decisions on the basis of models that work well only at the population level, but that is what doctors do. I also find it frustrating that these models haven't been refined for people who are BRCA negative. All BC risk models draw from the general population, including those at extremely high risk from BRCA, so in theory, if you know you're BRCA negative, the risk models are overestimating your risk to some degree (who knows how much).

There are tests beyond BRCA for gene mutations that have some relationship to breast cancer. The trouble is that only a handful of those mutations have any clinical guidelines for management; the testing technology is way ahead of our knowledge of what to do with the information. I'd love to get tested for only the genes for which there are clinical guidelines, but Myriad and the other labs seem to wrap them all up in a (pricey) package. So additional testing could give you some guidance, or it could just leave you with a source of worry and no direction.

The biggest clinical question at my risk level is whether to do screening MRIs every year or every two years. Starting this routine young virtually guarantees harm from false positives, over diagnosis and over treatment. (I've already experienced this end of it, and it sucks). My doctors told me it was my decision. This "punting" thing doctors do has been criticized too. http://www.nejm.org/doi/full/10.1056/NEJMms1409003

I guess the best thing is to find the best expert you can -- preferably a geneticist with a focus on BC genes who is really up on the research and who understands the predictive value, and the limits, of each of those models.

Best of luck to you.

farmerlucy,

I thought that Chek2, combined with positive family history, was also a pretty high risk situation? This is one that concerns me, as a person with Eastern European ancestry.. I can't recall if there is a formal clinical guideline for this scenario.

I am looking into having my mom's DNA banked for future testing, in the hope that testing her DNA may be a cheaper and more direct way to predict risk for both me and my sister in the future when we have more data about these mutations. Insurance coverage for testing is likely to lag the science, so if I'm paying out of pocket for these tests, better for my sister and I to split the bill.

Banking is cheap. You might consider this place, mentioned to me by my GC (I have no affiliation or interest):

https://www.preventiongenetics.com/dna-banking/dna...