M. Dowsett et al., Antiproliferative effects of idoxifene in a placebo-controlled trial in primary human breast cancer, CLIN CANC R, 6(6), 2000, pp. 2260-2267
Idoxifene is a novel selective estrogen receptor modulator, It has reduced
agonist activity on breast and uterine cells compared with tamoxifen and an
tiproliferative effects in tamoxifen-resistant breast cancer cells. Previou
s studies have shown that a short course of treatment with other antiestrog
ens prior to surgery caused a significant reduction of the growth fraction
when measured by immunohistological staining using the mouse monoclonal ant
ibody Ki67. In this study, we assessed the effect of idoxifene on biologica
l markers of cell proliferation (Ki67) and apoptosis (TdT-mediated dUTP-bio
tin nick end labeling), and estrogen and progesterone receptor (ER/PR) expr
ession was also evaluated. Core-cut biopsies were obtained in 77 postmenopa
usal patients with primary breast cancer at diagnosis. Patients were random
ized to 40 mg/day idoxifene or placebo for 14-21 days prior to obtaining a
second biopsy sample at surgical resection, The percentage of Ki67-positive
cells fell from a mean 19.7 +/- 2.7% (SE) to 13.4 +/- 3.4% in idoxifene-tr
eated ER-positive turners (n = 30; P = 0.0043), but there was no significan
t effect in placebo-treated ER-positive tumors (n = 27). No effect was seen
on ER-negative tumors in either group, Idoxifene had no significant effect
on apoptotic index but produced a statistically significant fall in idosif
ene-treated ER immunohistochemical score and a small increase in PR that di
d not reach statistical significance (0.05 < P < 0.10). Idoxifene was well
tolerated in all patients. Idoxifene has an antiproliferative effect in ER-
positive but not ER-negative breast cancers, and no significant effect on a
poptosis in the short-term.