Genomic Alterations Testing

I had Foundation One testing done.  In fact it was done without my knowledge.  I found out when I received a letter from the Lab stating they were billing my insurance. My MO has NEVER discussed the results with me.  I got on Foundation One website and asked for a copy of my results.  They sent it to me.  But how do you read it???  HELP!!!  

Thanks Grannax2 for starting this thread. 

Grannax - I don't understand if your Foundation One testing said you do or do not have ERBB mutation. Not sure of your dx ILC or IDC but maybe this article may be pertinent:

It's a hard read, but basically some ILCs can mask a mutation that is HER2+ even if pathology shows HER2- therefore additional targeted therapies might be a benefit.

There is a thread on this that I started until ILC - the woman who replied to my initial post knows the details of this condition. You may want to reach out to her.

Good idea to contact F1. My MO gave me the first few pages of the report only. I am curious about what else was included.

Grannax, stable is great news! Congrats.

The way I understood it, alterations / amplifications like ESR1 show that one's body has activated or has the potential to activate another pathway for the cancer to grow, which means the cancer *may* use another option for feeding itself without having to rely on estrogen. It doesn't necessarily happen right away and in some cases, never happens. It is not a hard and fast or black and white rule and many people with these mutations respond to hormone therapy for a good, long run of time. Also, it is a moving target as the body switches on and off certain pathways from time to time. Many who became resistant to hormone therapy later became resensitized to it after a long chemo run or after taking high dose estrogen as a therapy. Also with ER+ BC, there is a fair amount of periodic self-deactivation seen. Certain mechanisms of ER+ BC send signals that cause the cancer cells to deactivate and go into hybernation for long periods of time. It is a complex set of factors. I wouldn't quit a treatment that is working based on a particular mutation. I would just watch it more closely. At least 3 of my mutations are considered to highly correlate with hormone therapy resistance but Tamoxifen kept my early stage cancer at bay for 8 years and I lasted over a year on my first line metastatic hormone therapy, despite having super aggressive BC from the get go.

Although Abemaciclib, another CDK inhibitor, shows activity as a single agent treatment, clinical trials with Ibrance did not have the same success without use in combination with hormone therapy.

JFL ... looks like we have a lot in common in terms of dx and treatment.. A little over a year agowas diagnosed at 37 while pregnant and was stage 4 from the get go with mets to liver and bones. I tried many treatments in such a short time but nothing seems to keep working.. I tried letrezole and ibrance, abraxane and Xeloda.

I’m currently thinking of doing more genetic testing to seek more targeted treatment.. I heard about the Caris test but now I’m reading about the F1 tests from this thread.

Do you recommend doing that? Did any of you actually were successful in finding a treatment that works based on such tests?? I heard that even if they recommend treatment, if is not a standard breast cancer treatment then that’s basically hitting a wall if you can’t afford treatment on your own as insurance won’t cover non standard or not studied treatments.

I’m on the virge of giving up and just go palliative (I hate this word btw), but I’m worried of getting weak, fractured and immobile again! I’m having a hard time going through more failures.. this emotional roller coaster is too much for me. I’m trying not to give in to these thoughts especially when I see my older kids and the baby but I’m not sure what to do.

Alot of you seem to have a grip over this .. I look up to you and hope I can find some guidance:)

So, I apparently have the most boring metastatic breast cancer in town. No relevant mutants found, low TMB of 1 muts, no PD-L1, no microsatellite instability, 0% TILs.

The MO was frustrated because it means there are fewer unconventional approaches to try, but also said it is likely the sign of a less aggressive cancer (even though it is clearly capable of metastasis).

For those of you showing more mutations, was the test done on a biopsy taken after some/ a lot of treatment? I wonder if my tumor is just typical for a naive tumor and a higher mutation burden generally shows up in response to treatment. I asked the doctor and he wasn't sure. Said we will think about retesting in the hopefully distant future when the treatments start failing

I can't offer any clinical advice, but I can explain the terms in your report if you are interested.

Three mutations were found: ESR1-DS58G (pretty sure that should be ESR1-D558G), GATA3-M357fs, and SPEN Y596fs. The first part is the affected gene, so you have mutations in three genes: ESR1, GATA3 and SPEN. The second part is the "street address" of the mutation within the gene: the first letter tells you the altered amino acid, the middle number is the position on the gene (the house number if you like), and the last letter is what the amino acid was changed to. So for example in ESR1 the code for amino acid D (Aspartic Acid) was changed to amino acid G (Glycine). The GATA3 and SPEN mutations are slightly different: the 'fs' means frameshift which is a deletion that has altered the reading frame of the DNA and completely knocked out the gene.

MS-stable and TMB- intermediate are measurement of overall genome stability. The details are complex.

And now you know!

Grannax, thanks for the feedback. I agree with you, boring is a great start point. I'm sure that even the simpleton cancers learn a few tricks along the way as they are subjected to therapy, so I really hope mine is also a slow learner .

Great job outsmarting yours for 25 years - hope there are at least as many to come!