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Fulvestrant Reduces Cell Turnover Index More Than Tamoxifen

Fulvestrant Reduces Cell Turnover Index More Than Tamoxifen

SAN FRANCISCO—A new measure to evaluate the effect of preoperative
antiestrogen agents on tumor growth in early estrogen-receptor (ER)-positive
breast cancer suggests that fulvestrant (Faslodex, ICI 182,780,
investigational) is superior to tamoxifen (Nolvadex). Fulvestrant is an
estrogen-receptor downregulator and is considered a pure antiestrogen.

The new measure, cell turnover index (CTI), takes into account both cell
proliferation and apoptosis, according to investigator Nigel J. Bundred, MD,
consultant surgeon, South Manchester University Hospital, Manchester, UK.

Tumor growth is a balance between cell proliferation and cell death, Dr.
Bundred said at the 37th Annual Meeting of the American Society of Clinical
Oncology (ASCO abstract 1660). While both cell proliferation and apoptosis
rates are used separately as endpoints in drug trials, they are biologically
linked in tumors. "Clearly, drugs that lower proliferation but increase
apoptosis are desirable," he said.

While the study purpose initially was to confirm preliminary findings that
fulvestrant has different biologic effects in breast tumors than tamoxifen,
researchers also wanted to determine if CTI is a better method for analyzing
drug effect on tumors. CTI is measured by a log transformation after dividing
the proliferation index (measured by Ki67 immunostaining) by the apoptosis
index (measured by TUNEL staining).

Dr. Bundred and his colleagues used data from a randomized,
placebo-controlled trial comparing three doses of a preoperative single
intramuscular injection of fulvestrant (50 mg, n=39; 125 mg, n=38; 250 mg,
n=44) with preoperative tamoxifen (20 mg daily for 14 to 21 days, n=36) in
women with early operable ER-positive breast cancer.

Dr. Bundred’s earlier reports had shown that both tamoxifen and
fulvestrant (125 mg and 250 mg) significantly reduced proliferation, compared
with placebo, but did not significantly alter apoptosis (despite a 16% rise in
median apoptotic index for Faslodex 250 mg, compared with baseline).

In the current study, Dr. Bundred reported that both tamoxifen and
fulvestrant reduced proliferation in the tumors, compared with placebo. There
was a significant rise in apoptosis with fulvestrant against tamoxifen, but not
against placebo.

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