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.