[JessicaV]

Hi Ann, Thanks for sharing your story in full here. It is an amazing story and you are a truly amazing woman. I wish you NED and a long and happy life.

I hope you don't mind me putting my oar in here, but there is one aspect of how HER2+ breast cancer works that you mention but what you say is really unclear to me. It is an area that is not understood by many people. It is how people become resistant to the HER2+ targeted therapies/humanised mouse antibody drugs like Trastuzumab.
You say:
I had my brain tumor tissue tested a month ago by Foundation One, facilitated by my naturopathic oncologist. I do not show any genes of resistance to targeted therapies.

Could you explain what you mean by "genes of resistance to targeted therapies?" because this does not make sense to me in view of how I understand that resistance to these therapies occurs?

As I am sure we all know, these drugs work by blocking off the HER2+receptors so that human growth factor cannot attach to the receptors and thus cannot activate pathways involved in various aspect of tumor growth, invasive change, and spread etc. Blocking the process at this level prevents the activation of the next level of signalling pathways.
"Becoming resistant" to these drugs means that the tumor cells have mutated (i.e. have developed different daughter cells that the drugs cannot damage in the same way. The tumor cells may for example have truncated HER2+ receptors that Trastuzumab cannot block off, or changed in other ways that enable them to now continue to function or partly function despite the presence of the anticancer drug which killed the original tumor cells. They divide these into 3 groups:

Pathway redundancy—the ability of a signaling pathway to remain activated, despite being inhibited by a targeted therapy;

Escape pathways—in this scenario, even if the signaling pathway is inhibited, a cell could recruit an alternate signaling pathway and escape the effects of a targeted therapy; and

Pathway reactivation—essentially, the ability of a cell to reactivate the signaling pathway via mutations within the downstream receptor layer, despite the presence of inhibitory therapy.

But the part few people are aware of is that these mutations are not determined by your own genes or by the genes of the tumor cells. They are new forms that come into being because some of our tumor cells are stem-cell-like, and are thus able to alter their own genes to new pattern not contained in our own genomes or in the genes of the original tumor cells. This means they can form daughter-cells that are different to their own, which can then become a new proto-type tumor cell that flourishes because it is not affected by the trastuzumab.

How does this relate to the testing of your tumor for genes of resistance?

This is scary, but I understand this is part of why they found that adding Perjeta to Herceptin had a better result: it blocked more signalling pathways, so it is harder for the tumor to come up with mutations that are not already being blocked.
Please check out this research article as it seems to be really on the money with a real message of hope for all of us as far as I can see:
Curr Stem Cell Res Ther. 2015;10(3):271-82.
Role of flavonoids in future anticancer therapy by eliminating the cancer stem cells.
Sak K1, Everaus H.
This is a fascinating bit of research about tumor stem-cells, in which the researchers also identified that there are substances in common foods that also help to destroy tumor stem-cells in particular isothiocyanates and sulforaphane in broccoli and other cruciferous vegetables, soy, curcumin in turmeric, Epigallocatechin-3-gallate (EGCG) in green tea. I will paste the abstract on the end of this post.
Abstract
Despite the numerous recent advances made in conventional anticancer therapies, metastasis and recurrence still remain the major problems in cancer management. The current treatment modalities kill the bulk of the tumor, leaving cancer stem cells behind and therefore, the agents specifically targeting this cancer initiating cell population may have important clinical implications. In this review article, the data about the inhibitory action of flavonoids, both natural as well as their synthetic derivatives, on the self-renewal capacity and survival of cancer stem cells of different origins are compiled and analyzed. These data indicate that several plant secondary metabolites, including soy isoflavone genistein, green tea catechins and a widely distributed flavonol quercetin, have the potential to suppress the stemness markers and properties, traits of the epithelial-to-mesenchymal transition and migratory characteristics, being also able to sensitize these cells to the standard chemotherapeutic drugs. These polyphenolic compounds act through multiple signal transduction pathways, providing thus the maximal therapeutic response and offering some promise to be included in the future cancer treatment schemes in combination with the conventional therapies. Such approach may give an important contribution to the shift of cancer management from palliative to curative mode, likely leading to the disease-free survival. Thus, flavonoids can serve as attractive candidates for novel anticancer agents by eliminating the roots of cancer.