In reply to a previous post inquiring about the Herceptin activity on primary tumours (
Effect Of Herceptin On Primary Tumour) the majority of responders implied that only chemo would cause regression (to allow less invasive surgical excision).
However one responder,Taffy, described an extraordinary quick & pronounced regression (from "orange to golf ball" size to use her terms).
She stated that in addition to newly prescribed Herceptin she was taking Anastrozole & fish oil pills (as well as occasional iron supplements). Her onc who was surprised by the sudden effectiveness of Herceptin stopped the previously prescribed chemo regimen.
This raised many questions about why Herceptin was so effective in her particular case. Is it a fortunate unexplainable single case or is there a plausible reason to suspect that either Anastrozole &/or fish oil pills may be additive to the effectiveness of Herceptin in a larger number of patients?
Some light on the possible effect of Anastrozole is shed by the comments in 2004 by Dr Kent Osborne
(http://www.breastcancerupdate.com/bcu2004/4/osbourne.htm) were he stated (extracted):
Estrogen deprivation in HER2-positive, ER-positive breast cancer
As predicted based on model systems, estrogen deprivation has been shown to be beneficial in HER2-positive, ER-positive tumors. Even though such tumors have numerous estrogen receptors in the membrane and nucleus, and high growth factor signaling, if the estrogen receptors are not activated with a ligand such as tamoxifen or estrogen, neither of these pathways are activated.
A few years ago people doubted the results of Matt Ellis' study in which letrozole produced a much higher response rate than tamoxifen in patients with HER2-positive disease because the study involved a small number of patients. However, Mitch Dowsett's IMPACT trial has shown that another aromatase inhibitor — anastrozole — is also much better than tamoxifen in these patients. In practice, when HER2 is overexpressed, estrogen deprivation may be a better choice than tamoxifen — either an oophorectomy in younger women or an aromatase inhibitor in older women.
Tamoxifen resistance and the conversion of tumors from HER2-negative to HER2-positive
We have laboratory and clinical data suggesting that tamoxifen can convert a tumor from HER2-negative to HER2-positive (Figure 3.1). In an in vivo model using a cell line with low EGFR and HER2, we've shown that initially, tamoxifen has antiestrogenic activity on the tumor. However, after three or four months tamoxifen resistance develops, and tamoxifen acquires the ability to stimulate the tumor
It may be to evaluate the merits of combining Anastrozole & Herceptin that a clinical trial in Europe is underway as mentioned in the 2006 interview with Dr mark Pegram (
http://www.medscape.com/viewarticle/520710 ):
Medscape: How important are the identified pathways, such as HER-2, in hormone receptor-positive patients?
Dr. Pegram: I think they are critical because of receptor cross-talk between receptor tyrosine kinases, such as HER-2, EGFR [epidermal growth factor receptor], or IGF [insulin-like growth factor] receptors. All of these have been implicated in the emergence of steroid hormone independence, and, if that is the case, then we need to exploit that receptor cross-talk pathophysiology and target it specifically. For example, letrozole plus or minus lapatinib is being studied in a large randomized phase 3 registrational trial. The study size is powered so that we will be able to critically evaluate even the HER-2-positive subset in this cohort. I see this as the first really serious effort to test this receptor tyrosine kinase steroid receptor cross-talk hypothesis in a pivotal clinical trial. There are other such randomized trials under way in Europe, for example, with anastrozole plus or minus trastuzumab. My understanding is that this study was almost presented this year at San Antonio, but they are several events shy of their first planned interim analysis. I am very anxious to see that study presented, perhaps at ASCO 2006. It is a small study, only about 100 patients per arm, so it is really more like a randomized phase 2. Therefore, I don't think it will be definitive, but it might give us some clues as to what to expect in the larger studies with similar designs.
Let's hope that the trial findings are going to be positive for the majority of patients.
In the meantime can we find out if there are other forum members who are taking Herceptin plus an aromatase inhibitor such as Letrozole, anastrozole etc..? With what results on primary & mets tumours?