Cell proliferation in normal human breast ducts, fibroadenomas, and other ductal hyperplasias measured by nuclear labeling with tritiated thymidine. Effects of menstrual phase, age, and oral contraceptive hormones

Abstract

The proliferative rates of terminal duct cells were studied by tritiated thymidine labeling in vitro in 104 specimens of benign breast tissue from 92 women, The tritiated thymidine labeling index showed a cyclic pattern consistent with regulation by female sex hormones. It was low during the segment of the menstrual cycle encompassing days 2 through 15 (early cycle) and often was elevated during the segment encompassing days 16 through 1 (late cycle). The early cycle geometric mean index for morphologically normal terminal ducts was 0.19,and for ducts of fibroadenomas it was 0.77. The geomitric means for latecycle were 1.03 and 1.67 respectively. The difference for normal ducts between early and late cycles was highly significant (p less than 0.001). For both normal ducts and fibroadenomas the tritiated thymidine labeling index correlated negatively with the age of the patient, and the higher index value of fibroadenoma ducts relative to normal ducts was entirely accounted for by the younger mean age of the fibroadenoma patients. Oral use of contraceptive hormones could not be shown to change the index in either normal ducts or fibroadenoma ducts. Based on a postulated duration of DNA synthesis of 12 hours, the mean turnover time of the cells of normal terminal ducts would be approximately 22 days for 20 year old women with regular menstrual cycles, and would increase to 147 day at age 40. The mean potential doubling times of fibroadenomas would be approximately 33 days. The index values of other benign ductal proliferative lesions of the breast were similar to those of fibroadenomas and normal terminal ducts.