The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology

• Published in: Human reproduction (Oxford) 2008-09, Vol.23 (9), p.2072-2079
• Main Authors: Engman, M., Skoog, L., Söderqvist, G., Gemzell-Danielsson, K.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biopsy; Biopsy, Fine-Needle; Birth control; Breast - cytology; Breast - drug effects; Breast - pathology; Breast cancer; breast epithelium; Cell division; Cell growth; Cell proliferation; Cell Proliferation - drug effects; Cellular biology; Cytology; Double-Blind Method; Endometrium; Epithelial cells; Epithelium; Estrogens; Female; fine needle aspiration cytology; Gonadal Steroid Hormones - blood; Gynecology; Gynecology. Andrology. Obstetrics; Hormone Antagonists - adverse effects; Hormone Antagonists - pharmacology; Hormone replacement therapy; Humans; Hydrocortisone; Ki-67 Antigen - analysis; Laboratories; Mammography; Medical sciences; Menopause; Menstrual Cycle - drug effects; Menstruation; Mifepristone; Mifepristone - adverse effects; Mifepristone - pharmacology; Obstetrics; Post-menopause; Premenopause; Progestin; proliferation; Surgery; Testosterone; Ultrasonic imaging; Womens health
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/den228

BACKGROUND Progestins as well as estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of mifepristone on cell proliferation in human breast tissue in vivo was studied in premenopausal women. METHODS A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses. RESULTS The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P = 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased. CONCLUSIONS The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.