• Prévention

  • Chimioprévention

  • Sein

Clinical Trial of Acolbifene in Premenopausal Women at High Risk for Breast Cancer

Mené sur 25 femmes présentant un risque élevé de cancer du sein avant la ménopause, cet essai évalue la possibilité d'utiliser l'acolbifène, un modulateur sélectif des récepteurs à œstrogènes, pour réduire le risque de développer la maladie

he purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. In order to do so we assessed change in proliferation in benign breast tissue sampled by random periareolar fine needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia +/- atypia and {greater-than or equal to}2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8 months, and then had benign breast tissue and blood risk biomarkers re-assessed. Ki-67 decreased from a median of 4.6% (interquartile range, 3.1 - 8.5%) at baseline to 1.4% (IQR, 0.6 - 3.5%) after acolbifene (P<0.001; Wilcoxon signed rank test), despite increases in bioavailable estradiol. There were also significant decreases in expression (RT-qPCR) of estrogen inducible genes that code for pS2, ER-

α, and PgR (p

≤0.026). There was no significant change in serum IGF-1, IGFBP3, IGF-1:IGFBP3 ratio, or mammographic breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen inducible gene expression but minimal side effects, suggesting a Phase IIB placebo-controlled trial evaluating it further for breast cancer prevention.

Cancer Prevention Research

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