A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment

Abstract

Objective To use the fine-needle aspiration (FNA) biopsy technique to compare the effects of tibolone, conventional hormone replacement therapy (HRT) and placebo on breast cell proliferation in postmenopausal women.

Methods A total of 91 women were randomized to receive either estradiol 2 mg plus norethisterone acetate 1 mg (E₂/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody.

Results From the 83 women who completed the study, a total of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were evaluable for MIB-1 content. Women with assessable biopsies were younger, had a lower body mass index, and had higher levels of sex hormone binding globulin and insulin-like growth factor-I than women in whom the cell yield was insufficient. During treatment with E₂/NETA, there was an increase in proliferation (percentage of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No significant changes were recorded during treatment with tibolone or placebo. There was a negative association between proliferation and serum levels of total (r_s = −0.29, p < 0.05) and free (rs = −0.31, p < 0.03) testosterone.

Conclusions Tibolone seems to have little influence on breast cell proliferation.

• BREAST CELL PROLIFERATION
• HORMONE REPLACEMENT THERAPY
• TIBOLONE
• FINE-NEEDLE ASPIRATION CYTOLOGY