Effect of Treatment with 4-Hydroxyandrostenedione on the Peripheral Conversion of Androstenedione to Estrone and in Vitro Tumor Aromatase Activity in Postmenopausal Women with Breast Cancer1

The effect of treatment with the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) on the peripheral conversion of androstenedione to estrone has been examined in eight postmenopausal women with advanced breast cancer. Before treatment conversion of androstenedione to estrone (|P]BB')ranged from 0.81 to 3.7% and was almost completely inhibited after treatment with 4-OHA (two doses of 500 mg i.m. with an interval of 12 days between doses). Transfer constants were also measured by the urinary method (Mm" ) for some subjects and decreased from 2.3 ±0.52% to 0.24 ±0.11% after treatment, a mean reduction of 90%. Mean plasma concentration of estradici (37.4 ±16.6 pmol/liter) and estrone (99.0 ±32.2 pmol/liter) decreased significantly (P < 0.01) to 15.7 ±4.6 pmol/liter and 52.4 ±8.9 pmol/liter, respectively, after treatment. Aromatase and DNA polymerase a (a marker of cell prolif eration) activities were measured in seven samples of breast tumor tissue obtained before and after treatment. For three samples there was a marked (67 ±17%) decrease in tumor aromatase activity after treatment, for two, little change occurred, while tumor aromatase activity in the other two samples appeared to be resistant to the effect of 4-OHA. The correlation between tumor aromatase and DNA polymerase oractivities (r = 0.45) failed to reach a significant level.