The effect of tamoxifen on PCNA expression in fibroadenomas.

Abstract

For almost three decades, tamoxifen has been used in the adjuvant treatment of breast cancer. It has also proven effective in the chemoprophylaxis of this disease and in the treatment of cyclic mastalgia. Since a fibroadenoma is a benign hormone-dependent neoplasm which contains estrogen receptor (ER) levels higher than in the mammary lobule, an evaluation of the effect of this drug on the proliferative activity of both the epithelium and the stroma of fibroadenomas in premenopausal women following the administration of 10 or 20 mg/day over 22 days was proposed. Forty women with fibroadenoma were selected for a randomized double-blind trial. They had regular menstrual cycles and had received neither hormones nor become pregnant 12 months prior to this study. Patients were divided into three groups: A (n = 14; placebo), B (n = 13; tamoxifen 10 mg/day), and C (n = 13; tamoxifen 20 mg/day). The treatment was initiated on the first day of their menstrual cycle and the surgeries were performed on the 22nd day. Estradiol, progesterone, and steroid hormone binding globulin (SHBG) were measured twice. The first measurement was performed on the 22nd day of the previous menstrual cycle and the second one was performed on the day of surgery. The fibroadenoma was fixed in 10% formaldehyde solution and stained with hematoxylin and eosin and then processed through immunohistochemical reaction (PC-10, DAKO code number M879, Denmark A/S). The immunoexpression of the proliferative cell nuclear antigen (PCNA) of at least 500 epithelial and 500 stromal cells was evaluated. Such cells were interactively counted using the Kontron Imaging System KS-300 computerized analysis system, with x 400 magnification. As to PCNA expression in the fibroadenomas' epithelium, the average percentage of stained nuclei in groups A, B, and C was 25.2, 19.3, and 18.0, respectively. However, no significant difference was found in the variance analysis of these data (p = 0.168). As to the study of the fibroadenomas' stroma, the average percentage of stained nuclei found in groups A, B, and C was 32.4, 23.2, and 18.4, respectively. The variance analysis (p = 0.031) and Fisher's multiple comparison test (1.39; 26.67 confidence interval [CI]) confirmed that the number of PCNA-expressing nuclei in the stroma was significantly lower in group C (20 mg/day) compared to group A (control). However, there was no significant difference between group B (10 mg/day) and group C (20 mg/day). It was found that tamoxifen reduced the expression of PCNA in the epithelium and the stroma of the fibroadenoma. However, the effect was only statistically significant in the stroma when a 20 mg/day dose was administered.