The gross cystic disease fluid
protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating
glycoprotein tumor marker for
breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced
breast cancer suggested that
androgen therapy could cause significant increases in plasma levels in the absence of
disease progression. In order to evaluate the frequency, time course, and intensity of the
androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV
breast carcinoma were treated with
fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and
carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during
therapy. By day 6 of
therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the
glycoprotein during the first six days of
therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human
breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by
androgen, but not by
estrogen. From these data, we conclude that
androgens can specifically stimulate secretion of GCDFP-15 by
breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of
tumor growth.