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MommaCJ, Thanks for all that information!!! We're always very interested in whatever UCLA finds interesting!

I will look up the first trial and come back, but wanted to weigh in on what CBL was saying, keep the BRIA-IMT trial on your list for future because wow if you can get the tumor mutation burden to jump up 10 points that alone would be worthwhile because the recent trial Sara Tolaney did for MBC showed TMB over 14 they saw a 60% response rate for immunotherapy, and those were with ER-positive MBC, the "coldest of the cold cancers"… Anything that can give us a potential new line of therapy, esp something that the cancer hasn't seen before, is obviously a great help! I wish somebody would study this and see if this is something that BRIA-IMT does particularly, or its just random that it happens? On my Guardant and Foundation One reports the TMB went up incrementally from 1 to 10 and now one report says 39, so it can just go up over time in response to treatment I suppose? During this time the cancer also developed ESR1 and PIK3CA mutations, and the latter at least is associated with higher tumor mutation burden. There is very little information about how TMB develops or changes, but its good to know to keep an eye on that.

The other point you raise is also really interesting. These PIK3CA treatments usually lead to a big drop in PIK3CA-mutant cells in the Guardant test, and I've seen where the fraction of ESR1 mutations may also go down, but don't know why that would be. Its a similar situation in Her2-low cancers, where treatment with Enhertu reduces the Her2 levels significantly in like a third of patients. Of course the mutant cells are still around but in much lower numbers. So I've wondered if that means one would be less likely to respond to PIK3CA or Her2 therapy in the future, and maybe its not something that can be predicted because one can get a good response even if the level is not high. But obviously it would be helpful to have any data addressing that question, and doctors would have had some experience with that by now.

We are so very sorry to hear of Kris's passing, though we know it is a relief for her. Kris was a steadfast, incredibly loved and helpful member of our community and will truly be missed dearly. She gave so much to our family here and we grieve with you and all who loved her. Sending gentle hugs.

—The Mods

@threetree about histotripsy, I know someone in my clinic who had it done. 5 out of 6 liver tumors responded, but one got enlarged after procedure, and she also had a few new progressions elsewhere, which I believe are unrelated to histotripsy (maybe because she was out of Xeloda for a couple of weeks or so, IDK just a thought). Regarding the tumor that didn’t respond, there’s been some debate. a researcher at a teaching hospital commented that histotripsy might not be a complete treatment for breast cancer metastases since these tumors can be very solid, and the waves may not always destroy them fully. but I think it really depends on the tumor’s location and size. for example, if it’s large and deep under the chest cage, the waves might not reach it effectively. It’s probably a good discussion to have with your IR or MO.

my MO is very old school, he’s opposed to to any new treatment including experimental one like histotripsy, last year when I brought it up before I had Y90, he hadn’t even heard of it!