Effects of tamoxifen and CV 205502 on the morphology and the evolution of the noncancerous mouse mammary gland.

Tamoxifen (TAM, 0.01 mg/animal, three times a week) and the experimental prolactin-lowering CV 205502 (CV, 1 microgram/animal, daily) were administered prophylactically, alone or combined, to virgin C3H/Sy mice during the early period of promotion in this spontaneous mammary carcinogenesis system (end of 2nd-5th month of age), in order to study their influence on the morphology and evolution of the noncancerous mammary gland during therapy and after treatment cessation. During TAM administration the epithelial cells of the growing part of the gland exhibited myoepithelial- and, late in the treatment period, apoptotic-like features instead of the secretory ones expected, accompanied by intense basement membrane alterations, thickening of the surrounding connective tissue and arrested adipocyte maturation. These effects reversed progressively after drug withdrawal. The epithelial alterations were more intense and longer lasting in the TAM+CV-group, while growth arrest of the glands was observed in both groups parallel to the degree and the duration of these morphological changes. In these groups, tumor incidence was diminished, as expected, but the tumors that developed late after treatment cessation were of low histological differentiation. The above morphological observations show that TAM inhibits noncancerous mammary gland growth during the reproductive period by altering stromal and epithelial differentiation, effects that reverse progressively after treatment discontinuation and are potentiated by a prolactin-lowering agent in this animal study.