[Lani]

I prefaced the posting of the abstract with my opinion that its conclusions do not, in my humble opinion, hold.

I think there are several types of er+her2+ breast cancer not just one, so drawing conclusions based on separating her2+ breast cancer into er+ and er- may be misleading.

In this paper, they found that er+ breast cancers may not respond equally well to her2 targeted agents (despite the fact that neither the North American nor the HERA adjuvant herceptin trials came to that conclusion) and that they may respond to agents targeting PI3K/AKT (there are several in development, but none near FDA approval as far as I can tell from having attended the AACR annual meeting in mid-April).

They noted that adding an "estrogen receptor inhibitor" to a PI3K/AKT inhibitor may even worsen the outcome, as would using an "estrogen receptor inhibitor" alone. I can only guess that they mean tamoxifen as an estrogen receptor inhibitor as AIs work in a different way ie, inhibiting formation of the ligand for the estrogen receptor ie, estrogen. Fulvestrant is not an estrogen receptor inhibitor either as it degrades (destroys) the estrogen receptor.

I hesitated to post this as it is a summary of a paper given, so no way to check out the details and I knew those who were treated only with tamoxifen without herceptin might panic.

However, in light of the recently discussed problems with her2 testing and the retrospective nature of this study (vs. the prospective nature of HERA and the North American study), I would take this study with a grain of salt and utilize it as a spring-board to motivate one to look up other studies on the behavior differences between er+ and er- her2+ breast cancer and subtypes being found within er+ breast cancer.

This paper raises all kinds of questions, but answers none.

Why did I post it?

To remind people that unfortunately herceptin alone doesn't work for all so research is necessary to find out why (and how we can remedy that), to remind people that
there is oversimplification as to how many types of her2+ breast cancer there are and how each behave, to point out to people that there are pathways besides er and her2 which may become the driving force in a particular breast cancer and need blocking, and to remind people that the 5 subtypes of breast cancer (normal type, her2 type, luminal A type and luminal B type and basal type)
classification we now have is not all inclusive and leaves a lot of questions about er+her2+ breast cancer.
THe good news--just around the corner is a method to look at INDIVIDUAL circulating tumor cells (or those in bone marrow) and determine which pathways are active. With that knowledge, treating early by blocking the
three or so most active pathways simultaneously with agents effective against cancer stem cells, may allow shorter courses of more effective treatment and prevent dormant stem cells from launching a recurrence later or subclones of resistant cells from benefiting from lack of competition for resources.