Metabolism and Tissue Uptake of Estrogen in Women with Advanced Carcinoma of the Breast¹

Abstract

An exploratory study was made of the dynamics of estrogen metabolism and tissue uptake in 9 postmenopausal women with advanced breast cancer. Estrone-6,7-3H (in 9 experiments) and 17β-estradiol-6,7-3H (in 1 experiment) were infused intravenously at a constant rate in a physiological range. A steady state was, however, difficult to approach even after many hours of continuous infusion except in patients with normal liver function. In such patients, the metabolic clearance rate for estrone (2 experiments) was 2117 and 2360 1/day; for 17β-estradiol (1 experiment), it was 766 1/day. The clearance of estrogen from plasma was much slower in the 2 patients studied who had extensive metastases to the liver with ensuing jaundice; however, estrogen metabolism was unimpeded in other respects. The plasma radioactivity was chiefly conjugated in infusion experiments with estrone-6,7-3H, but almost equally distributed between the free and conjugated fractions in an experiment with 17β-estradiol-6,7-3H. In contrast to plasma, free radioactivity predominated in the following peripheral tissues: breast tumor, metastatic lymph node, noncancerous breast, adipose tissue, skeletal muscle, and skin. There was a marked uptake of free radioactive estrogen in breast tumor, metastatic lymph node, noncancerous breast, and adipose tissues. The uptake was most striking in an experiment with 17β-estradiol-6,7-3H with respect to the primary breast tumor and particularly the secondary tumor (in a lymph node). The concentration of free radioactive estrogen was of the order of 10−9 moles/kg (or liter) wet tissue in plasma, breast tumor, and a metastatic lymph node. Radioactive estrone and 17β-estradiol were the major free estrogens present in plasma. The pattern of free estrogen radiometabolites in breast tumor, noncancerous breast, and adipose tissues was essentially similar to that in plasma.