Epithelial proliferation in the normal human breast in relation to endogenous hormones and oral contraceptive use

We studied proliferative activity in the breast tissue from 40 healthy premenopausal women who underwent reduction mammoplasty. Twenty-four women had regular menstrual cycles; 16 were taking combined oral contraceptives. Lobuloalveolar tissue was examined by means of the Ki-67/MIB 1 antibody to identify proliferating cells. The number of positive-staining cells was related to the estimated number of cells to form an activity ratio (AR). We found a significantly higher AR in the secretory compared with the proliferative phase of the menstrual cycle, and a tendency for higher AR values in late compared with early oral contraceptive treatment cycles. In multivariate analyses, the secretory phase was associated with a significantly higher AR, and oral contraceptive use was associated with a higher AR than natural cycles. Our data suggest that progesterone/progestins augment proliferation in the normal breast epithelium and highlight the complexity of cell regulatory factors affected by exogenous steroids.