Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue

Objectives: To investigate the proliferative activity of the mammary gland epithelium and plasma levels of progesterone, estradiol, prolactin, luteini zing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-bindi ng globulin (SHBG) in premenopausal women treated with 10 and 20 mg of tamo xifen (TAM) for 22 days. Patients and methods: A randomized double-blind st udy was performed with 43 premenopausal women with a diagnosis of fibroaden oma of the breast. The patients were divided into three groups: A (n = 15, placebo); B (n = 15, TAM 10 mg/day) and C (n = 13, TAM 20 mg/day). They sta rted taking an oral dose of TAM or placebo on the very first day of the men strual cycle. Lumpectomy was performed on the 22nd day of therapy. Normal b reast tissue samples were collected during surgery, immediately immersed in 10% buffered formalin, processed for routine histology and immunohistochem istry for proliferating cell nuclear antigen (PCNA) detection. Two peripher al blood samples were collected, both on the 22nd day of the menstrual cycl e, in order to evaluate the hormone levels. PCNA expressing epithelial cell s were quantified by using a digital program Kontron Image System KS-300 in 1000 cells (400 x). Results: The percentage of cells expressing PCNA was s ignificantly higher in the group receiving placebo (group A, 50.3%) when co mpared to groups receiving TAM 10 or 20 mg/day (group B, 24.1%; and group C , 23.2%, respectively) (P < 0.001). Differences between groups B and C were not significant. Levels of progesterone, estradiol and SHBG were significa ntly higher in B and C groups compared to group A. Increasing concentration s of FSH (P < 0.0045) and lower levels of prolactin (P < 0.0055) were only found in the group receiving 20 mg/day of TAM (group C). Conclusions: A 22- day TAM therapy, either with 10 or 20 mg/day, significantly reduced the PCN A expression and therefore the proliferative activity of the normal human b reast tissue. Increasing levels of estradiol, progesterone and SHBG were as sociated with TAM therapy at 10 or 20 mg/day. However, a significant change of the level of FSH and prolactin was reached only with a 20-mg/day dose. (C) 1999 International Federation of Gynecology and Obstetrics.