Resistance to Herceptin: any comments?

[heblaj01]

A number of articles posted by several members have delt with resistance to treatment drugs.

For instance, Tamoxifen after being ineffective for 3 months has been found to cause or enhance progression to HER positive status.
Chemo drugs at normal or high doses stop working as cytotoxic agents but are still usable in frequent low doses as antiangiogenesis drugs.

Targeted drugs like Herceptin (& possibly Lapatinib) while working efficiently over long periods (years in some patients) on specific HER positive cells can nevertheless cause what some researchers call "crosstalk" in some patients. This word, is borrowed from the jargon of the telephone transmission industry where it indicates one voice channel interfering with an other channel due to insufficient electronic isolation (two conversations heard on the same telephone line).
In the case of the targeted drugs it seems to indicate that while HER+ cells continue to be affected the same cells (or others?) are becoming ER positive
& the disease starts to progress leading to the use of the word "resistance".
But in some cases continued (or readministered) Herceptin treatment in spite of apparent resistance has shown some beneficial effects.
An other possible factor is insufficient PTEN before or following Herceptin treatment.

This is confusing,at least to me.
I would appreciate comments from other members who have a better understanding of what is going on in the case of Herceptin when it appears to become less effective.

Two clinical trials in progress may provide some answers:
-a large Herceptin+Femara phase III trial
-a Herceptin+Faslodex phase I trial

Femara suppresses estrogen almost fully but does not affect estrogen receptors on the surface of cancer cells leaving them still subject to "crosstalk" from Herceptin.
On the other hand, Faslodex degrades effectively estrogen receptors leaving ,in theory,no way for reappearance of ER+ cells.
As Dr Pegram remarked in an interview, because of the way Faslodex works it may provide the more interesting results in combination with Herceptin once this trial reaches phase III.

[R.B.]

I have done a lot of reading on the subject of fats, and this is my perspective from that viewpoint.

I can only make some general observations;

The body's systems are hugely subtle complex and interconnected like a giants cat cradle of enormous complexity.

The body is of necessity adaptive.

A huge range of things interact to allow cancers to grow.

As I understand it they are still not certain as to all the possible mechanisms by which Herceptin works.

On the HER issue are you confusing HER which is a growth factor with oestrogen ER. This confused me for ages too.

As I understand it

HER and ER are from totally different "families. HER2 belongs to one of four growth factors known by a variety of names. At least part of tumour growth is controlled by these growth factors.

Oestrogen is from a family of hormones.

If somebody could clarify how the family of growth factors communicate with oestrogen and the nomenclature it would be really helpful- i think I have begun to get an inkling of how it fits read some more and find myself uncertain again.

They both are relatively closely interconnected through the reproductive and related function.

It may be by blocking the different pathways of both a synergy is acheived.

I suppose at a pragmatic level there must be a logic is you have two approved drugs that work to varying extent for the same disease to try them together.

To know the rational one would have to see the basis of the trial.

So much from what I have seen simply is not known.

In a sense this is why I think it is equally important that money is spent looking at cause, and that patients do all they can to try and reduce risk though diet etc.

Oestrogen growth factors and fats are truly fundamantal to the reproductive process. If they assist with very many others in making new life they surely have to power when out of control to make a tumour. But which body factors is pulling which body factors (mechanisms) strings is the real question. A french biopsy trial showed a 69% risk reduction in lumps being invasive at excisions between the top third and lowest third of womens breast fat tissue level of DHA and EPA. This rattles in my head.

I have a huge number of questions but beyond saying - it is fundamental to balance the omega threes and sixes and ensure a supply of the long chain threes DHA and EPA - that DHA is reported as working in synergy with a number of chemos, that balancing the omega threes and sixes will reduce a tendancy to inflamation, and hopefully help improve the function of the immune system - I cannot answer your questions.

As usual please discuss dietary changes with your advisors. There are cases where blockages may lead on long chain omega six shortage. It is possible to have fat status tested.


RB