Aromatase in Human Breast Carcinoma1

Breast carcinoma tissue is capable of forming estrogens from circulating androgen precursors. In this study, aromatase was examined in homogenates of breast adipose and breast carcinoma tissue, in normal and abnormal parenchymal breast tissue, and in breast carcinoma cells in culture. Homogenates of carcinoma tissue showed a wide range of activity in the conversion of adrostenedione to estrone. The mean conversion in carcinoma tissue was greater than that seen in parenchymal tissue from patients with gynecomastia and mammary dysplasia. Homogenates of breast adipose tissue from patients with benign and malignant disorders showed comparable aroma tase activity. Three cell lines isolated from a primary breast carcinoma differed in their aromatase activity demonstrating a heterogeneity of aromatase activity in cells from a single tumor. Studies of aromatase activity in breast carcinoma cells in culture over a period of 8 hr demonstrated progressive estrone formation. Testosterone formation from androstenedione was noted in all studies using both homogenates and cell cultures. Testos terone formation from androstenedione was approximately 10fold greater than was the formation of estrone from andros tenedione in all studies. The metabolism of androstenedione to other androgens examined in homogenates of normal and carcinomatous breast tissue revealed that the major products were androsterone, 5/8-androsterone, dihydrotestosterone, and epiandrosterone. Both estrogen and androgen formation within the cell may be important in determining the cellular response.