and it's a bear to read. It's a retrospective study of Her1, her2, er, and pr status and tamoxifen resistence in women treated with tamoxifen only
by Arpino, et. al.
http://jncicancerspectrum.oxfordjour...nci;97/17/1254
In summary, our findings support the hypothesis that loss of PR in ER+ breast cancer is a surrogate marker for increased growth factor receptor tyrosine kinase activity that causes lower PR expression and tamoxifen resistance in some patients. The results raise the possibility that overexpression of only HER-1 and/or HER-2 affects tamoxifen response substantially only when PR is negative. If PR expression is maintained, perhaps signaling through the HER family pathways is low despite overexpression of the HER receptors themselves. Although response to trastuzumab has not been shown to vary by ER status, if the hypothesis that lack of PR expression is a reflection of active signaling in the HER family is correct, then the response to trastuzumab or other small-molecule HER-2 inhibitors might be different in the PR+ and PR– subsets, an idea that could be explored in ongoing adjuvant clinical trials. Finally, if the link between PR negativity and high growth factor receptor signaling can be confirmed as a cause of tamoxifen resistance, then therapies targeting the growth factor pathways in combination with tamoxifen should be investigated in patients with ER+/PR– tumors in future clinical trials.