"Third gene" linked to breast cancer

jessica749

Interesting.  I get happy when I read of new development/progress. But then I get sad. So much we don't know. Progress yes but so so much we don't know.  

http://www.nytimes.com/2014/08/07/health/gene-indi...

farmerlucy

Thanks for the info. Today at my 3 mo appt my onco discussed the Myriad myRisk test, and I decided to do it. I just checked the list and the Palb2 syndrome is on it. 

wallycat

can't open the link.

DiveCat

I was aware of the PALB2 link, but will have to go back to a GC as further testing I had showed I had some "suspected" risk variations on PALB2; but at time my GC said not enough was known about the risk to make any recommendations. I'd like to know more for my siblings at this point.

jessica749

re link sorry try this [link activated for you - Mods]

http://www.nytimes.com/2014/08/07/health/gene-indicator-breast-cancer-risk.html?ref=health

MelissaDallas

Jessica, hitting "return" at the end of your link after pasting it will make it clickable if you want to try editing.

ihatesnowihatesnow

http://www.nytimes.com/2014/08/07/health/gene-indicator-breast-cancer-risk.html?ref=health

ihatesnowihatesnow

we knew nothing of cancer stem cells 15 years ago

http://en.wikipedia.org/wiki/Cancer_stem_cell

Lojo

For those of you who have already had treatment, is the genetic testing of Palb, etc to inform familial risk or might it affect your own future treatment? I'm BRCA1/2 negative, but mom died of premenopausal BC. I haven't done any other genetic testing. My mom's two sisters have had no issues (both older than she, and have lived/are alive to their late 80s). I have no siblings, and have 2 sons. I'll ask my MO at next appt if he thinks more extensive genetic testing would be valuable.

farmerlucy

Melissa - thanks for the tip about pasting links. I have trouble with that too.

Lojo - I saw my onc this week and she suggested I get more genetic testing since my family history is so sketchy  - my BC risk is probably as mitigated as we can get since I had the BMX, but they can also show predispositions for other types of cancer. Mainly I did it to have information for DD. 

Check out this gene table from Myriad. I hope you can link to it, I had to sign in as a professional. 

https://www.myriadpro.com/myrisk/why-myriad-myrisk...

JohnSmith

The PALB2 gene has been known to be connected to BC for many years, although it's nice that the New York Times is bringing it back to the mainstream. There are some companies that do comprehensive genetic tests looking at multiple genes (other than just the BRCA gene). 

One of those tests is done by a California based company called Invitae. They look at the following genes for sequence changes and exonic deletions / duplications: 

ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, NBN, PALB2, PMS2, PTEN, RAD51C, SLX4, STK11, TP53. (I believe if you test positive for some of these genes [like the TP53 gene] than radiation therapy is frowned upon, since the radiation can cause new cancer.)

Anyway, the actual test by Invitae is called: "Women's Hereditary Cancers Panel". This test may or may not be covered by insurance, and I'd imagine is more often done on younger women who have had a childhood cancer and/or strong family history of cancer. Despite meeting our "out of pocket max", our insurance only paid a portion of the bill, since it was not considered part of our PPO "in network" insurance.

jessica749

Thanks mods and Melissa for making the link clickable. I did hit return, often send links in my emails (nearly daily!) so not sure why I had trouble with this…thanks.

The second sentence says that the gene and its 'association' with bc has been known for some years and that yes, many genetic tests also already screen for it.  The "news"  in the first sentence is that a new study puts its risk as "almost as much as BRCA1 and BRCA2". That's quite alot more than an association, or link. I found that noteworthy.

It certainly makes me want to go back and find out from my mother's doctor/mother's test, what exactly and specifically was she tested for besides BRCA about 7 years ago  (if anything). She was  just given the paper / company 'report' (many even have been Myriad) that states no BRCA.  Was this gene tested for back when my mom had her BRCA testing done?  It also makes ME want to go back to MSKCC and ask what, specifically, besides BRCA was I tested for when I had my testing done a few years ago.  My family has generations /same side bc, and sisters, children, nieces, and nephews, who might want to know. ;o) 

Thank you farmerlucy and john for linking to the private corporations whose websites detail the panel testing they now can do. It makes me realize its certainly not enough for my family  to know I and my mother are BRCA negative. I want to know at least if PALB2 has been tested for and if not, perhaps redo.

JohnSmith

move along. nothing to see here.

jessica749

Just a blood test, from what I remember!  My mom still alive so.... The places where we tested will likely be able to find out if PALB2 was tested, and what our result is. Or possibly my mom will retest.

Moderators

See what the Breastcancer.org Research News team has to say about this discovery:

Abnormal PALB2 Gene Increases Breast Cancer Risk More Than Previously Thought

lekker

In general, genetic tests looking for familial cancer syndrome gene mutations use blood or saliva - not tumor tissue.  Also in general, if anyone received BRCA results before last summer, you only were tested for BRCA as Myriad had a patent and they weren't testing for anything else at the time.  Exceptions include if you were part of a research study at an academic institution (although in recent years Myriad prevented even universities from releasing results to patients) or if you were tested for only the three Ashkenazi BRCA founder mutations with a company other than Myriad (other companies licensed that testing and I guess it's possible they tested for other mutations too).  I've mentioned the Broca panel from the University of Washington many times on these boards.  It is the most comprehensive panel although more doesn't always mean better.  If your GC recommends one panel over another, ask why.  Make sure it's because it's the best test for you and not because they have a contract with one lab over another.  Also, I posted a while back that some insurers are trying to use only labs that will make their findings available to researchers.  Myriad has by far the largest database of information about BRCA mutations, but since 2004 they have kept it all in house as "intellectual property."  This is relevant for all of the women who get a "variant of unknown significance" as it will not be until enough data is collected (and shared!) that they will find out if it's a harmful mutation or not.

farmerlucy

mods - excellent article and very understandable. Scary stuff.

lekker - very enlightening. - this gene stuff is BIG business.

jessica749

Yes my genetics counselor told me that in 2011 when I was tested BART was not done.  I never pursued it further because I didn't want to spend the  $800 out of pocket I'd have to pay. 

Why would you go directly to a lab; why not see an accredited genetic counselor and talk to them about it, seems they'd be more in a position (or should be) to know which labs/tests etc should then be ordered. I mean, great that you already know this one specifically. 

http://nsgc.org/p/cm/ld/fid=164

lekker

Kayb - I think any of the genes tested on UW's Broca panel can be ordered individually, but I have no idea how/if that changes the cost of testing.  Your onc might not know much about genetic testing (most don't beyond BRCA) so you could consider asking for a referral to a licensed genetic counselor (like jessica suggested) and he/she can really get into your history to see what testing might be applicable.  I understand why insurance companies limit paying for testing, but I don't understand why it can be hard to get them to pay for a referral in certain cases - your bilateral BC plus your mother's history should've earned you an automatic visit with a LGC (in my humble and non-professional opinion).

I think BART is now included in Myriad's panel test, but it was an add-on with their "Comprehensive" BRCAnalysis test - how comprehensive could it be when they were missing 8-12% of positives (according to a study by UW's Mary Claire King) by not including BART?  Again, a LGC should be able to explain to you what, if any, additional testing would be recommended, then you try to get insurance to pay for it.

farmerlucy

my onc said myriad would call if my.cost is over $375. They haven't and it has been close to two weeks. Hmmm 

jessica749

You know kayb and others this is in part why, when people go on about the choices women make (i.e  bmx vs lumpectomy when 'medically' lumpectomy will do…) I get irritated, sometimes. These generic, generalized statistics re secondary bc are cited to every single person!  As if we are the same.  Meanwhile, of course, we are each different individuals, and I, like you, had bc in my family (mother, maternal grandmother died of it) and I just cannot believe that the generalized statistics  geared to some post menopausal (average aged woman)  without a family history (as most people don't have a family history) could apply to me, as I was premenopausal and my family had a history!   There were many other reasons I made the choice I did, but that was part of it.  There are many genes that contribute to bc, no doubt. The thing is we don't know everything about all those genes, and what they need in order to express, etc. (The 'environment', nature vs nurture if you will).

Clearly, something genetic in your family IS going on.  Whether it's something that medicine will discover in your lifetime though, that's another story.  I think you should google the national genetic counselors' organization and get an accredited genetic counselor closest to you and see them for an appointment.  Your relatives' may have elevated risk that will help them receive additional screening that may be recommended. (For example, I saw a genetic counselor and even though we - me and mom - were negative for BRCA, the GC did a risk evaluation of my siblings and said their lifetime risk of bc was 25%…certainly helping to shock them into additional screening…for some of them with better insurance….)

Lojo

Jessica, I totally agree with you. I made my BMX decision based on family history (mom died from premenopausal BC, and had a recurrence in the other breast), I was 41 at dx, and had a lobular tumor completely missed by mammograms (which I'd had since I turned 35). The lifetime risk of a contralateral recurrence was quoted in the 10-15% range over 20+ years. I'm BRCA negative, but clearly there's something going on genetically. I don't like hearing that a 60 yr old with no family or identified genetic risk gets a BMX, though I do understand scanxiety. In the end we'll never know if we made the right call, but it certainly felt right at the time, and still does.

lekker

Kayb - yes, I firmly believe that anyone with a family or personal history of cancer should consider a conversation with a licensed genetic counselor.  Be prepared with as much family information as you have (including medical records if possible) for the LGC so he/she can figure out whether or not there's enough suspicion to offer testing.  You never have to go through with any tests that you don't want and keep in mind that just because a test is offered, it doesn't mean your insurance will cover it so check first.  The LGC will be interested in more than just cancer - heart disease, diabetes, smoking/drinking habits, skin markings, birth defects, age at menarche and menopause, dates for births and deaths, mental health issues, etc.  The more, the better!  Broca is up to almost 50 genes now.  I don't know if that's a good thing or not.  I don't know if all of the tested genes are "actionable" - meaning would you know what to do if you were found to have a mutation?  Something to ask your genetic counselor!  

JohnSmith

Very thorough reading on genes associated with breast cancer: Breast Cancer genetics

Also, the following was documented in 2007:
Variations of the BRCA1, BRCA2, CDH1, STK11, and TP53 genes increase the risk of developing breast cancer.
The AR, ATM, BARD1, BRIP1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, RAD50, and RAD51 genes are associated with breast cancer.

lekker

Kayb - there are other, known "high penetrance" mutations that would impact screening and potentially treatment decisions.  See http://www.cancer.gov/cancertopics/pdq/genetics/b... Your onc is not correct - if you were to learn that you have a mutation in TP53, CDH1, PTEN or any of the Lynch genes, you would at the very least be offered more frequent breast screening as well as earlier colonoscopies and closer gyn screening possibly.  Other prophylactic surgeries might be offered (gastrectomy for CDH1, colectomy and hysterectomy for Lynch, etc.) and radiation in any form is to be avoided with TP53.  Yes, BRCA 1&2 (and recently PALB2) are the most famous, but they are not the only known actionable mutations.

It's the moderate and low penetrance mutations that currently raise more questions than they answer. 

As far as family history goes, it might not be an issue.  I had very limited family history of cancer, but because I had two separate primary cancers diagnosed unusually young, I qualified for testing.  You had synchronous bilateral breast cancer which is unusual enough to cover at least a referral to a counselor by many insurance companies.  Good luck with your decision making process - none of this is easy.

farmerlucy

No go on the MyRisk test for me. Myriad is using the same code as the old Brca test so it looks like a duplicate test to BCBS. Myriad said they hope to have a new code for the "update" test this fall. I asked if they have a single test for the PALB2 and they don't, only the 25 gene test. 

lekker

Sorry about that kayb.  I get pretty fired up when I hear that someone is being denied access to genetic counseling or relevant testing. In this case, you were clear that you were working through the issues with your dr but I jumped to my own assumptions.  I apologize for my mistake.  

lekker

I agree!  It's hard when the science of gene sequencing is outpacing the understanding of what it all means.