Antiproliferative effects of idoxifene in a placebo-controlled trial in primary human breast cancer

Citation
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
Citations number
24
Categorie Soggetti
Oncology
Journal title
CLINICAL CANCER RESEARCH
ISSN journal
10780432 → ACNP
Volume
6
Issue
6
Year of publication
2000
Pages
2260 - 2267
Database
ISI
SICI code
1078-0432(200006)6:6<2260:AEOIIA>2.0.ZU;2-D
Abstract
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.