Interview
with Neil Love, MD from Breast Cancer Update for Medical Oncologists,
Program 4 2000
Play
Audio Below:
Dr.
Robertson: The down-regulation of estrogen receptor and progesterone
receptor was dose-dependent, first of all. We saw down-regulation
of ER, PGR and also the proliferation marker MIB1. So it was dose-dependant.
The second thing was that at the clinically used dose it gave you
a significantly greater down-regulation of ER than tamoxifen, even
with only two weeks of treatment. In fact, Faslodex at all three
doses gave you a significantly greater down-regulation of progesterone
receptor than tamoxifen did.
Dr.
Love: Does tamoxifen down-regulate the estrogen receptor?
Dr.
Robertson: Tamoxifen does decrease the expression of the estrogen
receptor on sequential biopsy but not as much as the pure antiestrogen
appears to do. Interestingly, as well, none of the antiestrogens
or the placebo — obviously, too — but none of the antiestrogens
— either Faslodex at its three doses or tamoxifen — appeared
to affect apoptosis. And that is different from previous literature.
There has been some experimental data to suggest antiestrogens in
some of the models did induce apoptosis — and there was a publication,
in fact a group which was part of the publication, which suggested
that in human breast cancer tamoxifen and also Faslodex may induce
apoptosis. That data was not a prospective study and it was based
mainly on review of available biological samples, and therefore,
it was perhaps not the strongest data, but it was all the data we
had at the time. The current study — which as I say was prospective,
200 patients, pre and non-treatment biopsies — did not show
any effect on apoptosis. Now, one’s got to also consider that
perhaps the timing of the samples was not right and perhaps we missed
the apoptotic window, but certainly from the data that we have from
that study it didn’t appear to. So, there’s some interesting
studies from that, but not enough time to see a biological effect
being turned into a clinical effect in terms of shrinkage of the
tumor. Although, I think that is a potential other indication for
a pure antiestrogen in the future, would be in the neoadjuvant situation.
Similarities
and distinctions in the mode of action of different classes of antioestrogens
[Review]. Wakeling,
A. E. Endocrine-Related Cancer. 7(1):17-28, 2000 Mar. No abstract
Approaches
targeted to estrogen receptors for treatment of tamoxifen-resistant
breast cancer: A brief overview. Terakawa, N. (Reprint available from: Terakawa N Tottori Univ,
Sch Med, Dept Obstet & Gynecol Yonago Tottori 683 Japan)..
Oncology. 59(Suppl 1):3-4, 2000. No abstract
Treatment
with the pure antiestrogen faslodex (ICI 182780) induces tumor necrosis
factor receptor 1 (TNFR1) expression in MCF-7 breast cancer cells. Smolnikar,
K.; Loffek, S.; Schulz, T.; Michna, H., and Diel, P. (Reprint available
from: Smolnikar K DSHS Cologne, Inst Morphol & Tumor Res Carl
Diem Weg 6 D-50927 Cologne Germany). Breast Cancer Research &
Treatment. 63(3):249-259, 2000 Oct. In process
Symposium
overview: Estrogens and antiestrogens in managing the patient with
breast cancer. Newman,
L. A.; Wood, W. C.; Sellin, R. V.; Morrow, M.; Vogel, C., and Singletary,
S. E (Reprint available from: Singletary SE Univ Texas, MD Anderson
Canc Ctr, Dept Surg Oncol 1515 Holcombe Blvd,Box 106 Houston, TX
77030 USA).. Annals of Surgical Oncology. 7(8):568-574, 2000 Sep.
In process
