Influence of estrogen metabolism on proliferation of human breast cancer.

In order to investigate the influence of estrogen metabolism on human breast cancer, estradiol 2- and 16 alpha-hydroxylase (2- and 16 alpha-OHase) activities were determined in the microsomal fractions of cancer tissues by using reverse phase HPLC. 2-OHase activity was detected in most cancer tissues and noncancerous tissues, but the activity was significantly lower in cancer tissues than in the paired noncancerous tissues (0.01 < p < 0.02). Interestingly the patients without lymph node metastasis had significantly higher 2-OHase activity in cancer tissues than those with lymph node metastasis (0.02 < p < 0.05). No correlation was observed between ER status and 2-OHase activity in cancer tissues. On the other hand, 16 alpha-OHase activity was detected only in one third of the breast cancer tissues examined. The activity was not significantly different from that in noncancerous tissues, although it was relatively higher in ER-positive cancer tissues when compared with that in ER-negative ones (0.05 < p < 0.1). Estrone sulfatase activity measured simultaneously in the cytosol fractions of some specimens was much higher in cancer tissues than in noncancerous tissues (0.02 < p < 0.05). We found, however, no correlation between estrone sulfatase activity and estradiol hydroxylase activity. Taken together, our results suggest that the increase in 2-OHase activity prevents the proliferation of breast cancer and that estradiol metabolism is regulated independently of the local biosynthesis of estrogen.