BRIP1+ - I had 2 breast cancers at age 45

CrawfordsMommy

I'm confused. I received my genetic testing results, and I'm BRCA1 and BRCA2 negative. I tested positive for BRIP1. The note that came with my results said that it is "not clinically significant". However, I've read on here and elsewhere that BRIP1 is a risk factor for breast and ovarian cancer. Now I am confused! Is it a bad gene or not?

FYI: I am 45 and had 2 cancers pulled out of me back in June (in 1 breast). I have a family history of breast cancer on my father's side.

Fortunately my insurance company has agreed to pay for total hysterectomy this fall after I finish chemo.

But I am worried now for my sister who is 37. Should she be concerned about the BRIP1 gene?

pboi

I have similar stats as you do. DCIS and IDC in one breast at 43. Tested negative for BCRA 1/2, but BRIP1 positive. After active treatment I chose to have my ovaries removed. And I have a younger sister and twin daughters I worry about.

I have searched for the same answers as you, and it appears this gene may cause an increased risk for breast/ovarian cancer. At this time I don't think they really know that much about this gene yet. When I got my results they didn't suggest I needed to do anything different. I pushed to have my ovaries removed for my own piece of mind. I have 3 young kids at home, and I felt like I needed to do everything possible to keep cancer away.

PB

BarredOwl

Hi CrawfordsMommy:

Do you have a very strong family history of uterine malignancy or is there a separate gynecological reason for your planned total hysterectomy (with removal of the uterus)? Is it possible that a bilateral salpingo-oophorectomy (removal of both ovaries and Fallopian tubes) would be adequate?

Regarding your new test results, only a genetic change that is known to confer significant risk of breast cancer or other cancers is definitively bad. Some types of genetic changes may not confer increased risk, or it may not be known if they do or not.

Various changes in a particular gene are not created equal:

- Some genetic changes are harmful and are referred to as "pathogenic" mutations. However, different pathogenic mutations in the same gene may confer different levels of risk for cancer or other conditions. The particular mutation and what is known about it must be considered.

- Some genetic variation in genes is normal (blue versus brown eye color), and these changes are sometimes referred to as "polymorphisms". There may be evidence that a particular change does not appear to confer increased cancer risk, based on clinical studies of families that carry that specific polymorphism and it may be considered "neutral".

- The risk associated with some genetic changes is unknown and these are called "Variants of Unknown Significance", also referred to as "variants of uncertain significance" or "VUS"). Such genetic changes have not been adequately characterized. So the associated risk could be near 0%, or some intermediate level, or near the highest level associated with other known pathogenic mutations. It is not known.

Are any of the above terms found in your report?

Something that "is not clinically significant" probably is not a "pathogenic" or deleterious variant, but there is not enough information here for us to tell, and you should seek professional advice

Will you be meeting with a Genetic Counselor to review the results of your test? If not, please strongly consider requesting a referral to a Genetic Counselor to discuss your results. Such a specialist can advise you about the type of BRIP genetic change found, whether adequate evidence is available about it to conclude that the change is "not clinically significant," and provide you with advice in light of your existing breast cancer diagnosis and any family history. (Occasionally, even in the absence of a pathogenic mutation, personal and family history alone may independently support enhanced surveillance and/or certain risk reduction measures.)

BarredOwl

CrawfordsMommy

Thanks BarredOwl! Actually I was never offered genetic counseling.

I have separate gynecological issues (not cancer related) that I've had multiple surgeries for, I have had PID on and off for 25 years, and have already lost both Fallopian tubes. None of my doctors gave me any push back this time when I asked for the hysto, unlike every other time I asked for it prior to breast cancer. I still get hormone therapy after the hysto though since I'm ER+.

BarredOwl

Hi CrawfordsMommy:

Don't hesitate to request a referral for genetic counseling to discuss your results. It should help you to understand your specific results and the implications (if any) for you (and other family members). It is also helpful to understand the limitations of the testing you received (what it does not mean and open questions that have not been answered by the testing).

Both NCCN and ASCO recommend genetic counseling, both pre-testing and post-testing. I think and hope you will find genetic counseling to be valuable and informative, as I did.

BarredOwl