here is a post of mine from 2/20:
Lani
Senior Member
Join Date: Mar 2006
Posts: 1,031
just read this today--lapatinib tends to work on EGFR, IGFR simultaneously
and reverse herceptin resistance. It was done on SKBr3 (her2+er-) but in its discussion opined that triple positive bc would probably need treatment with an her2inhibitor, IGFR inhibitor and ER inhibitor(?lapatinib+AIor faslodex?):
http://mct.aacrjournals.org/cgi/content/full/6/2/667
Lapatinib induces apoptosis in
trastuzumab-resistant breast cancer
cells: effects on insulin-like growth
factor I signaling
Rita Nahta, F. Esteva, et al
Abstract
The majority of breast cancer patients who achieve an initial therapeutic response to the HER2-targeted
antibody trastuzumab will show disease progression within 1 year. Thus, the identification of novel agents
that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical. In the current
study, we show that the dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase
inhibitor lapatinib induces apoptosis in trastuzumab-resistant cells derived from the HER2-overexpressing
SKBR3 breast cancer line. Lapatinib inhibited EGFR and HER2 signaling in resistant cells, blocking
activation of downstream Akt, mitogen-activated protein kinase, and S6 kinases and inducing expression of
p27kip1. Importantly, lapatinib also inhibited insulin-like growth factor I (IGF-I) signaling and growth-
promoting effects in parental and resistant cells, and the cytotoxic effects of lapatinib were further enhanced
by the IGF-I receptor–blocking antibody IR3. As increased IGF-I receptor signaling has been implicated in
trastuzumab resistance, our data strongly support further study of lapatinib as a potential therapeutic in
breast cancers that have progressed on trastuzumab. [Mol Cancer Ther 2007;6(2):667–74]
I have also found an article that herceptin is thought to be as effective in
her2+er+s as in her2+ ER-s--as those patients who are early bc (less than stage 4) were all required to get chemo before/with herceptin, it will not be until some of the European trials of Herceptin/AIs without chemo (I believe I have read/heard that some may be starting at least on a neoadjuvant basis with chemo given after) show some results that anyone will be able to venture an opinion. I don't think anyone has looked at those who were not made permanently menopausal by the chemo perse.
Hope some of this helped!