Abstract
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 to 38 ± 13 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (>82 ng/ml) basal levels had marked (⩾75%) increases in 6/6 (100%) cases, whereas patients with low (<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-15in 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.
References
Haagensen Jr DE, Mazoujian G, Dilley WG, Pedersen CE, Kister SJ, Wells Jr SA: Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein. J Natl Cancer Inst 62: 239–247, 1979
Haagensen Jr DE, Mazoujian G, Holder WD, Kister SJ, Wells Jr SA: Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients. Ann Surg 185: 279–285, 1977
Haagensen Jr DE, Ammirata S, Cox E, Dilley WG, Wells Jr SA: Utilization of plasma marker proteins for detection and monitoring therapy in metastatic breast carcinoma. In Schwartz GF and Marchant D, (eds). Breast Disease Diagnosis and Treatment. Elsevier North Holland, New York, 1981, pp 301–325
Silva JS, Leight Jr GS, Ammirata S, Haagensen Jr DE, Tallos PB, Cox EB, Dilley WG, Wells Jr SA: Quantitation of response to therapy in patients with metastatic breast carcinoma by serial analysis of plasma gross cystic disease fluid protein and carcinoembryonic antigen. Cancer 49: 1236–1242, 1982
Haagensen Jr DE, Ammirata S, Dilley WG, Wells Jr SA: Tumor markers for detection of occult metastasis during the disease-free interval after mastectomy. Surg Forum 31: 433–435, 1980
Dilley WG, Leight Jr GS, Silva JS, Ammirata S, Haagensen DE, Wells Jr SA: Androgen stimulation of gross cystic disease fluid protein and carcinoembryonic antigen in patients with metastatic breast carcinoma. J Natl Cancer Inst 70: 69–74, 1983
Dilley WG, Haagensen DE, Wells Jr SA: Use of the gross cyst disease fluid protein assay in the management of patients with carcinoma of the breast. Ligand Rev 3: 12–15, 1981
Slot C: Plasma creatinine determination, a new and specific Jaffe reaction method. J Clin Lab Invest 17: 381–387, 1965
Horwitz KB, McGuire WL: Actinomycin D prevents nuclear processing of estrogen receptor. J Biol Chem 253: 6319–6322, 1978
Zava DT, McGuire WL: Human breast cancer: androgen action mediated by estrogen receptor. Science 199: 787–788, 1978
Allegra JC, Lippman ME, Thompson EB, Simon R, Barlock A, Green L, Huff CK, Do HMT, Aitken SC: Distribution, frequency and quantitative analysis of estrogen, progesterone, androgen, and glucocorticoid receptors in human breast cancer. Cancer Res 39: 1447–1454, 1979
Miller WR, Telford J, Dixon JM, Hawkins RA: Androgen receptor activity in human breast cancer and its relationship with oestrogen and progestogen receptor activity. Europ J Cancer Clin Oncol 21: 539–542, 1985
Carcinoembryonic antigen: its role as a marker in the management of cancer — National Institutes of Health Consensus Development Conference Statement. Cancer Res 41: 2017–2018, 1981
Bryan RM, Mercer RJ, Bennett RC, Rennie GC, Lie TH, Morgan FJ: Androgen receptors in breast cancer. Cancer 54: 2436–2440, 1984
Teulings FAG, van Gilse HH, Henkelman MS, Portengen H, Alexieva-Figusch J: Estrogen, androgen, glucocorticoid and progesterone receptors in progestin-induced regression of human breast cancer. Cancer Res 40: 2557–2561, 1980
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Dilley, W.G., Haagensen, D.E., Leight, G.S. et al. Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma. Breast Cancer Res Tr 8, 205–215 (1986). https://doi.org/10.1007/BF01807333
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DOI: https://doi.org/10.1007/BF01807333