Androgen-Estrogen Production Rates in Postmenopausal Women with Breast Cancer1

In an attempt to define the hormonal environment of women with breast cancer, we examined the blood pro duction rates of androstenedione and its contributory role as a prehormone of estrone in a group of 46 postmenopausal women with advanced metastatic breast cancer. Androstenedione blood production rates averaged 1.85 mg/day and were not significantly different from 9 agematched women with other neoplasms or from 4 noncancer controls. Similarly, blood production rates of estrone were not significantly different, averaging 56.9 /¿g/dayin women with breast cancer compared with 43.9 and 41.8 pig/day in the control groups. The blood transfer con stants (/>Ã-j¡) were again similar in the breast cancer women versus the 2 control groups (2.13% versus 2.35 and 2.74%, respectively). Despite the similar magnitude of androstenedione, es trone production rates, and transfer constants, andros tenedione conversion to estrone accounted for only 72% of the total estrone production rate in women with breast cancer versus 92 and 95% in the 2 control groups. These differences were significant at P < 0.05. As part of these studies, we noted that 14 of 46 women with breast cancer exhibited unusually high metabolic clearance rates of estrone ranging from 2600 to 5400 liters/day. These women could not be differentiated from other breast cancer patients on clinical grounds. Five patients had elevated clearance rates of androstenedi one, but testosterone and estradici clearance rates were not abnormal. Patients with the high metabolic clearance rates of estrone had lower plasma estrone concentrations so that blood production rates were similar to those noted in breast cancer patients with normal clearances. The differences in metabolic clearance rates were not associ ated with changes in the binding protein, sex hormonebinding globulin. We concluded that androstenedione production rates and conversion to estrone are normal in postmenopausal women with breast cancer and that estrone production rates are normal in these women, yet that approximately 30% of estrone produced in postmenopausal women with breast cancer comes from source(s) other than prehormonal androstenedione.