Age-related variations in growth kinetics of primary human breast cell cultures

Carcinogenic initiation in the mammary gland of experimental animals depends upon the presence of undifferentiated structures with a high rate of cell proliferation and short doubling time. To determine the influence of age on the presence of such structures in the human breast the following study was carried out. Normal breast samples were obtained from 8 patients undergoing biopsy for clinically benign lesions. Patients were separated into 2 groups: younger women (mean age 24±3 years) and older women (mean age 52±4.9 years). Histologically biopsies from the younger women contained mostly ductules and terminal ducts, while biopsies from older women contained mostly large ducts. Portions of the biopsies were digested with collagenase; epithelial cells aggregates were cultured in DMEM + Insulin + 15% Fetal Calf Serum. Growth of epithelial colonies was measured for up to 240 h or until confluence. Two different patterns of colony growth were observed: fast growing colonies (FGC) with a doubling time (dt) of 27.2±7.7 h, and slow growing colonies (SGC), with dt of 55± 12.5 h. Cultures derived from younger women consisted of 88% FGC and 12% SGC. In contrast, those derived from older women consisted of 17% FGC an 83% SGC. It is concluded that with aging, ductules and terminal ducts diminish in the breast, and with that the ductal cells predominate and replicate in vitro with longer doubling time.