Effects of tamoxifen on the breast in the luteal phase of the menstrual cycle

Abstract

Objectives: The effect of tamoxifen on cyclic mastalgia and on chemoprophylaxis against breast cancer is little known, mainly due to the difficulties in studying the normal human gland. We proposed to evaluate the mitotic index and the nuclear volume of the lobule of women medicated with tamoxifen only during the luteal phase of the menstrual cycle in order to observe the effect of tamoxifen on the normal human mammary gland. Methods: Twenty-four premenopausal women with fibroadenoma diagnosed via biopsy were studied. The phase of the cycle was determined by the date of menstruation and serum progesterone level in the luteal phase (≥3 ng/ml). The patients admitted to the study and were given written informed consent to participate in the investigation, which was previously approved of by the hospital Ethics Committee. Patients were divided at random into two groups: Group I consisted of 12 untreated women (control) and Group II consisted of 12 patients treated with 20 mg/day tamoxifen for 10 consecutive days beginning on the 13th day of the menstrual cycle. In both groups, the patients were submitted to biopsies of the nodule and of a 1-cm 3 fragment of adjacent mammary parenchyma between the 23rd and 26th day of the cycle. The mitotic index (number of mitoses/1000 nuclei counted) and mean nuclear volume (mean of 10 nuclear volumes for each case) were measured. Results: No mitosis was observed in Group II. There was a reduction in the mean nuclear volume in Group II (Mann–Whitney test). Conclusions: Tamoxifen, when administered only during the luteal phase of the menstrual cycle, significantly reduces the nuclear volume and mitotic activity of the epithelium. This data demonstrates an antagonistic action of tamoxifen on estrogen even when administered for short periods of time.