lonely in hboc-land, and i'm not sure what to do about it

fairylala

I'm really lonely in hboc land.

I'm very ashkenazi. I have a high, but unknown, lifetime level risk of breast cancer. While I haven't even gotten genetic testing yet, going into a room with other previvors, reading material about materials especially about previvors of asheknazi background, is starting to get exhausting and depressing.

The backstory is as follows

My grandmother, a holocaust survivor who got out of germany on the kindertransport, was diagnosed with breast cancer at roughly age 32. She either died of it metastasizing into her bones, or of bone cancer that may or may not be related[1], at around age 45, right before the 6 day war. My mother was 18 at the time.

My grandmother had 2 daughters, my mother and her sister, my aunt.

Both of them had breast cancer. First my mother, when I was in high school. Then my aunt, a few months after I graduated, while I was in israel for the year. My mother's was a triple negative tumor, laced with ER+ cells. My aunt's, I believe, was ER+ at the time of diagnosis. They got diagnosed about 3-4 years apart from each other, and both were below age 50 at the time of diagnosis. They were diagnosed and treated in the mid-2000s, right at the height of a lot of studies around brca and tumors, as well as the height of myriad's power. They both live less than 50 miles away from each other, are centerist orthodox ashkenazi jewish women, went to college, and even shop at the same butcher for the same cut of brisket for passover. Pre-cancer, my mother ate significantly healthier than my aunt, and exercised quite a bit more. My best understanding of the situation is they had fairly similar treatments according to the protocol at the time in two different hospitals, involving both chemotherapy and radiation.

My mother came out of the process way worse off than my aunt. My mother currently is more immunocompromised than my aunt, still has mild, permanent chemo-brain, and permanent joint issues. My mother, last I heard, has a thyroid tumor, very slow growing with some cancerous cells in it. Unlike my mother, my aunt is doing just fine.

At the time of my mother's diagnosis, not much was known about triple negative tumors, and even less was known about triple negative tumors that had a percentage of cells that were ER+, so she was enrolled in a genetics study. She came up BRCA negative. Despite this, she pressured my aunt to do genetic testing privately and to up her screening (which is why my aunt's cancer was caught). My aunt came up BRCA1 positive for a known ashkenazi variation.

When my aunt was finally diagnosed, my mother, my aunt, and my grandfather were approached to be part of a familial study.

My aunt still came up with her BRCA1 variant. Problematically, so did my grandfather.

My mother, again, still came up as BRCA negative, Despite her being ashkenazi, and 90% of familial breast cancer cases among ashekanazim walking through the door for treatment will have one of ashkenazi founder genes, my mother is not only not a carrier for those genes, she has a perfectly normal BRCA1 and 2 set.[2]

BRCA1 is a dominant gene, except in exactly one case, when it is part of the fanconi anemia cluster. It is also called in databases FANCS [3] The reason you never meet a person with 2 of the same BRCA1 mutations ((one for each chromosome), aka a FANCS triggered person with fanconi anemia due the BRCA1 gene, is a fetus who has both will spontaneously abort. It will never make red blood cells correctly, and can't survive.

My grandfather is a private person, and frankly, while I'm not orthodox now, growing up orthodox did mean talking about sex was not a thing people did. Still, children are highly valued in the orthodox world. Both of my maternal grandparents were holocaust survivors, and for them, having children would have been revenge of sorts. It would have been subtlety mentioned to me growing up if there had been problems for them conceiving, because they really wanted children. So while there is no explicit evidence my grandmother wasn't a BRCA carrier, chances don't look great either. And as a very dead person, she doesn't have a lot of genetic material around for us to test (unless my grandfather mysterious kept a comb of hers hidden away somewhere and no one realized it...)

So now there is me. I'm in this very awkward situation. I'm very close to my grandmother's age at diagnosis. It is technically impossible for my mother to give me a BRCA mutation. Even if I had the kind of insurance that right now would allow for genetic testing (I'm on medicaid while job hunting, and while counseling is covered, the testing isn't..weird), I currently don't have copies of my mother's genetic test results. Even if I had the copies, I would be stuck in one of two situations

1) because she was tested pre-myriad, she was tested on CLIA certified equipment in a CLIA-certified lab, doing the exact same work as myriad, but for experimental purposes only. At the time, any insurance company would have winked at and waved the fact it was experimental findings if I wanted testing, especially in light of myriad being the only commercial testing provider. Post-supreme court decision, it isn't clear that any insurance company would now accept those results as clinically valid, despite the fact that getting the same negative results twice is and then to find out later that she is BRCA positive would be a an extremely low probability event.

2) even if an insurance carrier suddenly decides to go back to accepting these results the way they did pre-myriad before the supreme court, what exactly are we testing for? My mother's cancer looks like BRCA cancer, plus she's ashekanzi. The problem is, that isn't occurring. which creates a ton more questions than answers. And those questions are emphasized by the presence of her sister who lives an extremely similar lifestyle, and who also had breast cancer and is a founder mutation carrier.

I assume, and to some degree some doctors I've spoken to, that if I tested I wouldn't get very meaningful results back. I read research. While there is some probability of suddenly discovering, say, my mother is a PALB2 carrier, one of the few benefits of being ashkenazi is usually there ARE founder mutations because we're seriously inbred, enough that scientists like recruiting us to actually find new genes (just as a starting point, because the genes you know you can rule out). My probability of carrying PALB2 or any other of the few remaining options is low.

With that assumption, comes a lot of problems. No one knows what my lifetime risk level is. For all I know, I have a lower lifetime risk level in absolute terms compared to other previvors, but if I get cancer, it is likely to come back and/or metastasize, based on the unknown family cause. This means preventative mastectomies are out because the absolute risks of complications from of a preventative mastectomy and reconstruction could be higher than my lifetime risk.

When talking to other previvors, other laypeople, and even non-specialist doctors, this story just sounds so crazy. I've had situations where I've explained this story to people 3 times in a row because it is so unusual. I even once had to explain to a resident going through a primary care fellowship 2x the statistics why he has to stop telling me to cut off my boobs and why it was medically inappropriate for him to give me this advice, because of how these risk profiles are developed and how I don't fit into them.

Furthermore, I feel like I am constantly surrounded by a community of people where because I'm in a really tiny minority, don't realize there is a lot of pressure to be a certain kind of previvor with a certain kind of background who makes certain kind of medical decisions. The media surrounding being a previvor talks a LOT about BRCA, they talk a LOT about preventative mastectomies and removing ones fallopian tubes, they talk to some degree about Lynch Syndrome, PALB2, and Hereditary Diffuse Gastric Cancer Syndrome. I never see coverage about previvors and their families who are OUTSIDE these criteria. The people where it is familial and just unknown. (Being ashkenazi and in this situation is super-duper isolating just because so much IS known and covered among ashkenazim)

As far as I know, there is only ONE other similar-ish family in the entire US. For a variety of reasons, I'm not becoming besties with my equivalents in that family. I'd (proverbially) kill to meet another. Or at least to know there are a community of women out there somewhere who are very high risk and are very constrained in their choices right now because we're the stuff experiments are made of, the stuff that science admits they don't know very much about

Are you here? Where are you? Or am I really just going to be alone for a long time?

[1]the discovery of olaparp and a lot of the testing on immunotherapy drugs is making it very clear that cancers of different parts of the body can be more related to each other than cancers of the same part of the body. Either way, she died of cancer.

[2] A small percentage of that remaining 10% have different BRCA genes. A small percentage of ashekanzim also have a high risk for Hereditary Diffuse Gastric Cancer Syndrome aka there is an ashkenazi variant of CDH1. There is also founder mutations for Lynch Syndrome as well. My mother has never been tested for either, but thanks to the holocaust, as far as we know, she also holds no family history for either. There is also currently no evidence among my cousins to think it might be a possibility. This puts her in a 2- 5% group total of people with family histories, have had cancer, are ashekanzi and no BRCA (and that probably me over-estimating)

[3] there was a link here to ncbi's gene database to brca1 just to show all the alternative possible names for BRCA1. I'm apparently to new to be allowed to post it.

vlnrph

I can't say I'm in the same boat however admire the logical way you look at and explain things! Good job on attempting to educate that resident. As you realize, research is always comingout with new findings. I assume you have a knowledgeable genetics counselor who keeps up to date on phenomena like rearrangement testing, etc.

Since you have not had BRCA analysis but with your family history would qualify, perhaps whatever insurance you get via a new job will allow a broader panel to be done. Even with low probability of having a mutation such as PALB2 or CDH1, it is possible and would be good to find out about. Most of us are alone, in one way or another...

Have you tried FORCE? The website and local support groups can be helpful even if their focus is on 'garden variety' versions of HBOC. Meanwhile, give your mom and aunt some hugs, also grandfather - he has certainly experienced much more than the average person, having all the females close to him suffer with this disease.

Moderators

Hi, FORCE is indeed a great suggestion. Also, have you reached out tohttp://sharsheret.org? This is their mission statement:

Mission Statement

Sharsheret is a national not-for-profit organization supporting young Jewish women and their families facing breast cancer. Our mission is to offer a community of support to women, of all Jewish backgrounds, diagnosed with breast cancer or at increased genetic risk, by fostering culturally-relevant individualized connections with networks of peers, health professionals, and related resources.